USE OF HEPARANASE TO IDENTIFY AND ISOLATE ANTI-HEPARANASE COMPOUND

Abstract: Purified heparanase having activity of greater than 20 units/ mu g protein, preferably greater than 50 units heparanase activity per mu g protein, is described. The use of heparanase for screening for anti-heparanase compounds is also described. In addition, the use of the high potency heparanase to accelerate wound healing or its use as an immobilized heparanase filter connected to extracorporeal devices to degrade heparin and neutralize its anticoagulant properties during surgery is disclosed.

Description: USE OF HEPARANASE TO IDENTIFY AND ISOLATE ANTI-HEPARANASE COMPOUND FIELD OF INVENTION The present invention discloses the use of mammalian heparanase, preferably recombinant heparanase, for screening for anti-heparanase compounds. More particularly, the present invention provides a method of selecting IHA (Inhibitors of Heparanase Activity). In addition, the present invention provides a purified heparanase, particularly suitable for use to identify and isolate anti-heparanase compounds as well as for other known uses of heparanases, such as its use to accelerate wound healing or its use as an immobilized heparanase filter connected to extracorporeal devices to degrade heparin and neutralize its anticoagulant properties during surgery. BACKGROUND OF THE INVENTION Elevated heparanase activity has been documented in mobile, invasive cells. Examples include; invasive melanoma, lymphoma, mastocytoma, mammary adenocarcinoma, leukemia, and rheumatoid fibroblasts. This activity has also been documented in non-pathologic situations involving the migration of lymphocytes, neutrophils, macrophages, eosinphils and platelets. An inhibitor of heparanase would therefore broadly influence the invasive potential of these diverse cells. Inhibition of heparan sulfate degradation would also inhibit the release of bound growth factors and other biologic response modifiers that would, if released, fuel the growth of adjacent tissues and provide a supportive environment for cell growth (Rapraeger, et al., Science 252: 1705-1708, 1991). Inhibitors of heparanase activity would be of value in the treatment of arthritis, vascular restenosis, tumor growth and progression, and fibro-proliferative disorders. Until now, the obstacles to designing a screening assay to find inhibitors of mammalian heparanase have been the unavailability of a mammalian heparanase that is purified to apparent homogeneity and the lack of information about the amino acid sequence or the 3-dimensional structure of the enzyme. Without the amino acid sequence, it has not been possible to produce recombinant mammalian heparanase to be used in large volume screening efforts. Knowledge of the tertiary and quaternary structures would facilitate rational design of IHA. This report overcomes obstacles relating to the sequence of the heparanase, and also provides a model for higher-order structure. Heparanase refers to a mammalian enzyme which can degrade heparin proteoglycans (HPG) and/or heparan sulfate proteoglycans (HSPG). Heparanase activity in mammalian cells is well known. It is found in various melanoma cells (Nakajima, et al, Cancer Letters 31: 277-283, 1986), mammary adenocarcinoma cells (Parish, et al, Int. J. Cancer, 40: 511-518, 1987), leukemic cells (Yahalom, et al, Leukemia Research 12: 711-717, 1988), mast cells (Ogren and Lindahl, J. Biol Chem. 250: 2690-2697, 1975), macrophages (Savion, et al, J. Cell. Physiol, 130: 85-92, 1987), mononuclear cells (Sewell, et al, Biochem. J. 264: 777-783, 1989), neutrophils (Matzner, et al, J. Leukocyte Biology 51: 519-524, 1992), T-cells (Vettel, et al, Eur. J. Immunol. 21: 2247-2251, 1991), platelets (Haimovitz-Friedman, et al, Blood 78: 789-796, 1991), endothelial cells (Godder, et al, J. Cell Physiol. 148: 274-280, 1991), and placenta (Klein and von Figura, BBRC 73: 569, 1976). WO 91/02977, incorporated herein by reference, describes a substantially, but partially, purified heparanase produced by cation exchange resin chromatography and the affinity absorbent purification of heparanase-containing cell extract. WO 91/02977 also describes a method promoting wound healing utilizing compositions comprising a "purified" form of heparanase. Others have proposed the use of purified bacterial heparanase, immobilized onto filters and connected to extracorporeal devices, to degrade heparin and neutralize its anticoagulant properties post surgery (Freed, et al, Ann. Biomed. Eng. 21: 67-76, 1993). U.S. Patent 4,882,318 describes heparanase-inhibiting compositions for preventing tumor metastasis. Haimovitz-Friedman et al. (Blood 78: 789-796, 1991) describe an assay for heparanase activity that involves the culturing of endothelial cells in radiolabeled 35 SO 4 to produce radiolabeled heparan sulfate proteoglycans, the removal of the cells which leaves the deposited extracellular matrix that contains the 35 S-HSPG, the addition of potential sources of heparanase activity, and the detection of possible activity by passing the supernatant from the radiolabeled extracellular matrix over a gel filtration column and monitoring for changes of the size of the radiolabeled material that would indicate that HSPG degradation had taken place. This assay does not have the capability for large-scale screening of inhibitors. Nakajima et al. (Anal Biochem. 196: 162-171, 1986) describe a solid-phase substrate for the assay of melanoma heparanase activity. Heparan sulfate from bovine lung is chemically radiolabeled by reacting it with [ 14 C]-acetic anhydride. Free amino groups of the [ 14 C]-heparan sulfate were acetylated and the reducing termini were aminated. The [ 14 C]-heparan sulfate was chemically coupled to an agarose support via the introduced amine groups on the reducing termini. This substrate is limited in that it is an extensively chemically modified form of naturally occurring heparan sulfate. Khan and Newman (Anal. Biochem. 196: 373-376, 1991) describe an indirect assay for heparanase activity. In this assay, heparin is quantitated by its ability to interfere with the color development between a protein and the dye Coomassie brilliant blue. Heparanase activity is detected by the loss of this interference. This assay is limited in use for screening because it is so indirect that other non-heparin compounds could also interfere with the protein-dye reaction. The CXC chemokine family (also called the intercrine α family) is one branch of the supergene "intercrine" cytokine family (Oppenheim, Ann. Rev. Bit :m. 9: 617-648, 1991). It's members include platelet factor 4, platelet basic protein and derivatives, γIP-10, gro(α,β,γ), NAP-l/interleukin-8, mig, and ENA-78 (for review, see Miller and Krangel, Critical Reviews in Immunology 12: 17-46, 1992). The other branch, the CC chemokines or intercrine-β family, includes MlPlα, MIPlβ,JE/MCP-l, RANTES, and MCAF. All members of both branches of this chemokine family characteristically are basic heparin-binding polypeptides, display molecular weights between 8 and 11 kD, share 20 - 50% homology, and function broadly in pathologic sit:.* ; ons characterized by inflammation and tissue remodeling. The prυicolytically processed forms of platelet basic protein include CTAP-m, β- thromboglobulin, and NAP-2. β-thromboglobulin (Moore, et al, Biochim. Biophys. Acta. 379: 360-369, 1975) and CTAP-III (Castor, et al, Arthritis Rheum. 20: 859-868, 1977), were originally isolated from activated supernatants or lysates from outdated pk ϊts. Using the techniques of subcellular fractionation and radioimmunoassay, β-thromboglobulin was identified as an α-granule protein that could be released upon activation (Kaplan, et al, Blood 53: 604- 618, 1979). Platelet basic protein itself was later isolated from fresh platelets, megakaryocytes, and HEL cells, an immortal human erythroleukemia cell line (Holt, et al, Biochemistry 25: 1988-1996, 1986; Holt, et al, Exp. Hematol. 16: 302-306, 1988). Walz and Baggiolini isolated the processed form of NAP-2 from platelet-containing cultures of stimulated mononuclear cells (Walz, et al, J. Exp. Med. 170: 1745-1750, 1989). Material labeled as β-thromboglobulin is commercially available from Calbiochem, San Diego, CA (Cat. # 605165), Celsus Laboratories, Cincinnati, OH (Cat. # 41705), and Haematologic Technologies, Essex Jet., VT (Cat. # HBTG-02100. The inventors have determined, by using the "Purification Assay," that the commercial preparation have heparanase activity at a level of 0.075 units/μg. This activity is below the level of 1 unit/μg needed for the screening of anti-heparanase compounds in accordance with the assay of the subject invention. U.S. Patent 4,897,348 describes recombinant materials and methods for producing human connective tissue-activating peptide-III (CTAP-III) and analogs thereof. Transglutaminases catalyze the posttranslational modification of proteins by transamidation of available glutamine residues. This action results primarily in the formation of epsilon-(gamma-glutamyl)lysine cross-links (Greenberg, et al, FASEB J. 5: 3071-3076, 1991). This posttranslational modification has been reported to dramatically alter the action of some small proteins. - For example, a transglutaminase produces a glutamine-lysine cross-link in the 13 kD phospholipase A 2 and increases its specific enzymatic activity (Cordella-Miele, et al, J. Biol. Chem. 265: 17180-17188, 1990). A transglutaminase cross-links another small molecule, interleukin-2, and converts its activity to one that is cytotoxic to mature oligodendrocytes (Eitan and Schwartz, Science 261: 106-108,1993). The glutamine-lysine cross-link in a protein would result in the loss of overall positive charge for that protein. The transglutaminases are optimally active and generally used under reducing conditions such as dithiothreitol. The concept that glutamine-lysine cross-linking alters the activity of these small proteins may be applicable to other small molecules as well. SUMMARY OF THE INVENTION The present invention discloses a method of screening for compounds having anti- heparanase activity (AHA compounds), i.e. inhibitors of heparanase activity (IHA), comprising the steps of: contacting a potential AHA compound with radiolabeled heparin heparan sulfate and heparanase for a time and under such conditions sufficient to allow for inhibition of heparanase activity; detecting inhibition of heparanase activity; and selecting compounds that inhibit heparanase activity. The present invention also discloses the amino acid sequence identity of the heparanase that has been purified to homogeneity by chromatography under reducing conditions. Identification of the amino acid sequence of the protein which contains heparanase activity is crucial for the production of recombinant mammalian heparanase. DETAILED DESCRIPTION OF THE INVENTION The present invention provides a purified heparanase, and a method for producing it. The heparanase so produced has an activity of greater than 20 units/ μg protein, preferably greater than 50 units heparanase activity per μg protein (1 unit = 1% cpm < 30 K/hr using the "Purification Assay" (Example 2, Part D). In addition, the present invention provides recombinant heparanase and a means for producing it. The term "purified heparanase" as used in the specification and claims includes the recombinant heparanase as described in the subject application. The recombinant heparanase of the subject invention can be used for the same purposes and in the same manner as the purified heparanase. The purified heparanase of the present invention has an isoelectric point of less than 5.5 (preferably about 4.8 - 5.1) and preferably is activated by treatment with transglutaminase using reducing conditions. The recombinant heparanase of the present invention has an isoelectric point of less than 5.5 (preferably about 4.8 - 5.1), and is isolated under reducing conditions and is activated by treatment with transglutaminase. Suitable transglutaminases that may be used for this purpose include Activated Factor Xma, guinea pig liver transglutaminase, epidermal transglutaminase, keratinocyte transglutaminase, and tissue transglutaminase. The heparanase of the present invention has the amino acid sequence (SEQ. ID. NO: 1) of: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala 5 10 15 Glu Leu Arg Cys Met Cys He Lys Thr Thr Ser Gly He His Pro Lys 20 25 30 Asn He Gin Ser Leu Glu Val He Gly Lys Gly Thr His Cys Asn Gin 35 40 45 Val Glu Val He Ala Thr Leu Lys Asp Gly Arg Lys He Cys Leu Asp 50 55 60 Pro Asp Ala Pro Arg He Lys Lys He Val Gin Lys Lys Leu Ala Gly 65 70 75 80 Asp Glu Ser Ala Asp 85 encoded by the cDNA sequence (SEQ ID NO: 2) of: 1 AACTTGGCGAAAGGCAAAGAGGAAAGTCTAGACAGTGACTTGTATGCTGA 51 ACTCCGCTGC ATGTGTATAA AGACAACCTC TGGAATTCAT CCCAAAAACA 101 TCCAAAGTTT GGAAGTGATC GGGAAAGGAA CCCATTGCAA CCAAGTCGAA 151 GTGATAGCCA CACTGAAGGA TGGGAGGAAA ATCTGCCTGG ACCCAGATGC 201 TCCCAGAATC AAGAAAATTG TACAGAAAAA ATTGGCAGGT GATGAATCTG 251 CTG AT which corresponds to the cDNA sequence and derived amino acid sequence of CTAP-HI. See Wenger et al., Blood, 73: 1498-1503, 1989. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 3) of: Ser Ser Thr Lys Gly Gin Thr Lys Arg Asn Leu Ala Lys Gly Lys Glu 5 10 15 Glu Ser Leu Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys He 20 25 30 Lys Thr Thr Ser Gly He His Pro Lys Asn He Gin Ser Leu Glu Val 35 40 45 He Gly Lys Gly Thr His Cys Asn Gin Val Glu Val He Ala Thr Leu 50 55 60 Lys Asp Gly Arg Lys He Cys Leu Asp Pro Asp Ala Pro Arg He Lys 65 70 75 80 Lys He Val Gin Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp 85 90 encoded by the cDNA sequence (SEQ ID NO: 4) of: 1 TCCTCCACCA AAGGACAAAC TAAGAGAAAC TTGGCGAAAG GCAAAGAGGA 51 AAGTCTAGAC AGTGACTTGT ATGCTGAACT CCGCTGCATG TGTATAAAGA 101 CAACCTCTGG AATTCATCCC AAAAACATCC AAAGTTTGGA AGTGATCGGG 151 AAAGGAACCC ATTGCAACCA AGTCGAAGTG ATAGCCACAC TGAAGGATGG 201 GAGGAAAATC TGCCTGGACC CAGATGCTCC CAGAATCAAG AAAATTGTAC 251 AGAAAAAATT GGCAGGTGAT GAATCTGCTG AT which corresponds to the cDNA sequence and derived amino acid sequence of platelet basic protein. See Wenger et al., Blood, 73: 1498-1503, 1989 as well as Walz and Baggiolini, BBRC 159: 969-981, 1989; Castor, et al, BBRC 163: 1071-1078, 1989. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 5) of: Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys 1 5 10 15 Met Cys He Lys Thr Thr Ser Gly He His Pro Lys Asn He Gin Ser 20 25 30 Leu Glu Val He Gly Lys Gly Thr His Cys Asn Gin Val Glu Val He 35 40 45 Ala Thr Leu Lys Asp Gly Arg Lys He Cys Leu Asp Pro Asp Ala Pro 50 55 60 Arg He Lys Lys He Val Gin Lys Lys Leu Ala Gly Asp Glu Ser Ala 65 70 75 80 Asp encoded by the cDNA sequence (SEQ ID NO: 6) of: 1 GGCAAAGAGG AAAGTCTAGA CAGTGACTTG TATGCTGAAC TCCGCTGCAT 51 GTGTATAAAG ACAACCTCTG GAATTCATCC CAAAAACATC CAAAGTTTGG 101 AAGTGATCGG GAAAGGAACC CATTGCAACC AAGTCGAAGT GATAGCCACA 151 CTGAAGGATG GGAGGAAAAT CTGCCTGGAC CCAGATGCTC CCAGAATCAA 201 GAAAATTGTA CAGAAAAAAT TGGCAGGTGA TGAATCTGCT GAT which corresponds to the cDNA sequence and derived amino acid sequence β-thromboglobulin (βTG). See Wenger et al., Blood, 73: 1498-1503, 1989. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 7) of: Glu Leu Arg Cys Met Cys He Lys Thr Thr Ser Gly He His Pro Lys 1 5 10 15 Asn He Gin Ser Leu Glu Val He Gly Lys Gly Thr His Cys Asn Gin 20 25 30 Val Glu Val He Ala Thr Leu Lys Asp Gly Arg Lys He Cys Leu Asp 35 40 45 Pro Asp Ala Pro Arg He Lys Lys He Val Gin Lys Lys Leu Ala Gly 50 55 60 Asp Glu Ser Ala Asp 65 encoded by the cDNA sequence (SEQ ID NO: 8) of: 1 GAACTCCGCTGCATGTGTATAAAGACAACCTCTGGAATTCATCCCAAAAA 51 CATCCAAAGTTTGGAAGTGATCGGGAAAGGAACCCATTGCAACCAAGTCG 101 AAGTGATAGCCACACTGAAGGATGGGAGGAAAATCTGCCTGGACCCAGAT 151 GCTCCCAGAATCAAGAAAATTGTACAGAAAAAATTGGCAGGTGATGAATC 201 TGCTGAT which corresponds to the cDNA sequence and derived amino acid sequence of neutrophil activating peptide-2. The foregoing amino acid sequences correspond to the products of a single gene called platelet basic protein (Walz and Baggiolini, BBRC 159: 969-981, 1989; Castor, et al, BBRC 163: 1071-1078, 1989). The complete gene sequence of platelet basic protein is well known. See, for example, Wenger et al., Blood, 73: 1498-1503, 1989 and Proc. Natl. Acad. Sci. USA, 90, 3660-3664, 1993. The present invention also provides heparanase having the amino acid sequences of other members of the CXC chemokine family [including Platelet factor 4 (SEQ. ID NO. 12), γIP-10 (SEQ. ID NO. 14), gro/MGSA (SEQ. ID NO. 16), gro- /MΣP-2a (SEQ. TD NO. 18), gf /'MIP-2β (SEQ. ID NO. 20), Interleukin-8/NAP-l (SEQ. ID NO. 22) and ENA-78 (SEQ. ID NO. 24)] as well as members of the CC chemokine family [including MlP-lα (SEQ. ID NO. 26), MlP-lβ (SEQ. ID NO. 28), 1-309 (SEQ. ID NO. 23), MCP-1 (SEQ. ID NO. 32), MC-3 (SEQ. ID NO. 34), RANTES (SEQ. ID NO. 36), fie (SEQ. ID NO. 38) and MCP-2 (SE*. * iD NO. 40)]; purified to apparent homogeneity, prepared in the presence of reducing conditions, and activated by treatment with transglutaminase. Suitable transglutaminases that may be used for this purpose include Activated Factor Xlϋa, guinea pig liver transglutaminase, epidermal transglutaminase, keratinocyte transglutaminase, and tissue transglutaminase. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 12) of: Met Ser Ser Ala Ala Gly Phe Cys Ala Ser Arg Pro Gly Leu Leu Phe Leu Gly Leu Leu Leu Leu Pro Leu Val Val Ala Phe Ala Ser Ala Glu Ala Glu Glu Asp Gly Asp Leu Gin Cys Leu Cys Val Lys Thr Thr Ser Gin Val Arg Pro Arg His He Thr Ser Leu Glu Val He Lys Ala Gly Pro His Cys Pro Thr Ala Gin Leu He Ala Thr Leu Lys Asn Gly Arg Lys He Cys Leu Asp Leu Gin Ala Pro Leu Tyr Lys Lys He He Lys Lys Leu Leu Glu Ser encoded by the cDNA sequence (SEQ ID NO: 13) of: 1 CCGCAGCATG AGCTCCGCAG CCGGGTTCTG CGCCTCACGC CCCGGGCTGC 51 TGTTCCTGGG GTTGCTGCTC CTGCCACTTG TGGTCGCCTT CGCCAGCGCT 101 GAAGCTGAAG AAGATGGGGA CCTGCAGTGC CTGTGTGTGA AGACCACCTC 151 CCAGGTCCGT CCCAGGCACA TCACCAGCCT GGAGGTGATC AAGGCCGGAC 201 CCCACTGCCC CACTGCCCAA CTGATAGCCA CGCTGAAGAA TGGAAGGAAA 251 ATTTGCTTGG ACCTGCAAGC CCCGCTGTAC AAGAAAATAA TTAAGAAACT 301 TTTGGAGAGT TAGCTACTAG CTGCCTACGT GTGTGCATTT GCTATATAGC 351 ATACTTCTTT TTTCCAGTTT CAATCTAACT GTGAAAGAAA CTTCTGATAT 401 TTGTGTTATC CTTATGATTT TAAATAAACA AAATAAATC which corresponds to the cDNA sequence and derived amino acid sequence of platelet factor 4. See Poncz et al., Blood 69, 219-223 (1987). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 14) of: Met Asn Gin Thr Ala He Leu He Cys Cys Leu He Phe Leu Thr Leu Ser Gly He Gin Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys He Ser He Ser Asn Gin Pro Val Asn Pro Val Asn Pro Arg Ser Leu Glu Lys Leu Glu He He Pro Ala Ser Gin Phe Cys Pro Arg Val Glu He He Ala Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys Ala He Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met Ser Lys Arg Ser Pro encoded by the cDNA sequence (SEQ ID NO: 15) of: 1 GAGACATTCC TCAATTGCTT AGACATATTC TGAGCCTACA GCAGAGGAAC 51 CTCCAGTCTC AGCACCATGA ATCAAACTGC GATTCTGATT TGCTGCCTTA 101 TCTTTCTGAC TCTAAGTGGC ATTCAAGGAG TACCTCTCTC TAGAACCGTA 151 CGCTGTACCT GCATCAGCAT TAGTAATCAA CCTGTTAATC CAAGGTCTTT 201 AGAAAAACTT GAAATTATTC CTGCAAGCCA ATTTTGTCCA CGTGTTGAGA 251 TCATTGCTAC AATGAAAAAG AAGGGTGAGA AGAGATGTCT GAATCCAGAA 301 TCGAAGGCCA TCAAGAATTT ACTGAAAGCA GTTAGCAAGG AAATGTCTAA 351 AAGATCTCCT TAAAACCAGA GGGGAGCAAA ATCGATGCAG TGCTTCCAAG 401 GATGGACCAC ACAGAGGCTG CCTCTCCCAT CACTTCCCTA CATGGAGTAT 451 ATGTCAAGCC ATAATTGTTC TTAGTTTGCA GTTACACTAA AAGGTGACCA 501 ATGATGGTCA CCAAATCAGC TGC- ACTACT CCTGTAGGAA GGTTAATGTT 551 CATCATCCTA AGCTATTCAG TAATAACTCT ACCCTGGCAC TATAATGTAA 601 GCTCTACTGA GGTGCTATGT TCTTAGTGGA TGTTCTGACC CTGCTTCAAA which corresponds to the cDNA sequence and derived amino acid sequelae- γIP-10. See Luster et al., Nature 315, 672-676 (1985). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 16) of: Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr Leu Gin Gly He His Pro Lys Asn He Gin Ser Val Asn Val Lys Ser Pro Gly Pro His Cys Ala Gin Thr Glu λ He Ala Thr Leu Lys Asn Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro He Val Lys Lys He He Glu Lys Met Leu Asn Ser Asp Lys Ser Asn encoded by the cDNA sequence (SEQ ID NO: 17) of: 1 CTCGCCAGCT CTTCCGCTCC TCTCACAGCC GCCAGACCCG CCTGCTGAGC 51 CCCATGGCCC GCGCTGCTCT CTCCGCCGCC CCCAGCAATC CCCGGCTCCT 101 GCGAGTGGCA CTGCTGCTCC TGCTCCTGGT AGCCGCTGGC CGGCGCGCAG 151 CAGGAGCGTC CGTGGCCACT GAACTGCGCT GCCAGTGCTT GCAGACCCTG 201 CAGGGAATTC ACCCCAAGAA CATCCAAAGT GTGAACGTGA AGTCCCCCGG 251 ACCCCACTGC GCCCAAACCG AAGTCATAGC CACACTCAAG AATGGGCGGA 301 AAGCTTGCCT CAATCCTGCA TCCCCCATAG TTAAGAAAAT CATCGAAAAG 351 ATGCTGAACA GTGACAAATC CAACTGACCA GAAGGGAGGA GGAAGCTCAC 401 TGGTGGCTGT TCCTGAAGGA GGCCCTGCCC TTATAGGAAC AGAAGAGGAA 451 AGAGAGACAC AGCTGCAGAG GCCACCTGGA TTGTGCCTAA TGTGTTTGAG 501 CATCGCTTAG GAGAAGTCTT CTATTTATTT ATTTATTCAT TAGTTTTGAA 5.51 GATTCTATGT TAATATTTTA GGTGTAAAAT AATTAAGGGT ATGATTAACT 601 CTACCTGCAC ACTGTCCTAT TATATTCATT CTTTTTGAAA TGTCAACCCC 651 AAGTTAGTTC AATCTGGATT CATATTTAAT TTGAAGGTAG AATGTTT " " 701 AATGTTCTCC AGTCATTATG TTAATATTTC TGAGGAGCCT GCAACATGCC 751 AGCCACTGTG ATAGAGGCTG GCGGATCCAA GCAAATGGCC AATGAGATCA 801 TTGTGAAGGC AGGGGAATGT ATGTGCACAT CTGTTTTGTA ACTGTTTAGA 851 TGAATGTCAG TTGTTATTTA TTGAAATGAT TTCACAGTGT GTGGTCAACA 901 TTTCTCATGT TGAAACTTTA AGAACTAAAA TGTTCTAAAT ATCCCTTGGA 951 CATTTTATGT CTTTCTTGTA AGGCATACTG CCTTGTTTAA TGGTAGTTTT 1001 ACAGTGTTTC TGGCTTAGAA CAAAGGGGCT TAATTATTGA TGTTTTCGGA which corresponds to the cDNA sequence and derived amino acid sequence of gro/MGSA (melanoma growth stimulatory activity). See Anisowicz et al., Proc. Natl. Acad. Sci. U.S.A. 84, 7188-7192 (1987). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 18) of: Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala Ala Gly Ala Pro Lys Ala Thr Glu Lys Arg Cys Gin Cys Lys Gin Thr Leu Gin Gly He His Leu Lys Asn He Gin Ser Val Lys Val Lys Ser Pro Gly Pro His Cys Ala Gin Thr Glu Val He Ala Thr Leu Lys Asn Gly Gin Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys He He Glu Lys Met Leu Lys encoded by the cDNA sequence (SEQ ID NO: 19) of: 1 CTCTCCTCCT CGCACAGCCG CTCGAACCGC CTGCTGAGCC CCATGGCCCG 51 CGCCACGCTC TCCGCCGCCC CCAGCAATCC CCGGCTCCTG CGGGTGGCGC 101 TGCTGCTCCT GCTCCTGGTG GCCGCCAGCC GGCGCGCAGC AGGAGCGCCC 151 CTGGCCACTG AACTGCGCTG CCAGTGCTTG CAGACCCTGC AGGGAATTCA 201 CCTCAAGAAC ATCCAAAGTG TGAAGGTGAA GTCCCCCGGA CCCCACTGCG 251 CCCAAACCGA AGTCATAGCC ACACTCAAGA ATGGGCAGAA AGCTTGTCTC 301 AACCCCGCAT CGCCCATGGT TAAGAAAATC ATCGAAAAGA TGCTGAAAAA 351 TGGCAAATCC AACTGACCAG AAGGAAGGAG GAAGCTTATT GGTGGCTGTT 401 CCTGAAGGAG GCCCTGCCCT TACAGGAACA GAAGAGGAAA GAGAGACACA 451 GCTGCAGAGG CCACCTGGAT TGCGCCTAAT GTGTTTGAGC ATCACTTAGG 501 AGAAGTCTTC TATTTATTTA TTTATTTATT TATTTGTTTG TTTTAGAAGA 551 TTCTATGTTA ATATTTTATG TGTAAAATAA GGTTATGATT GAATCTACTT 601 GCACACTCTC CCATTATATT TATTGTTTAT TTTAGGTCAA ACCCAAGTTA 651 GTTCAATCCT GATTCATATT TAATTTGAAG ATAGAAGGTT TGCAGATATT 701 CTCTAGTCAT TTGTTAATAT TTCTTCGTGA TGACATATCA CATGTCAGCC 751 ACTGTGATAG AGGCTGAGGA ATCCAAGAAA ATGGCCAGTG AGATCAATGT 801 GACGGCAGGG AAATGTATGT GTGTCTATTT TGTAACTGTA AAGATGAATG 851 TCAGTTGTTA TTTATTGAAA TGATTTCACA GTGTGTGGTC AACATTTCTC 901 ATGTTGAAGC TTTAAGAACT AAAATGTTCT AAATATCCCT TGGACATTTT 951 ATGTCTTTCT TGTAAGGCAT ACTGCCTTGT TTAATGTTAA TTATGCAGTG 1001 TTTCCCTCTG TGTTAGAGCA GAGAGGTTTC GATATTTATT GATGTTTTCA 1051 CAAAGAACAG GAAAATAAAA TATTTAAAAA T which corresponds to the cDNA sequence and derived amino acid sequence gro-β/Mff-2α (macrophage inflammatory protein 2-α). See Tekamp-Olson et al., J. Exp. Med. 172, 911-919 (1990). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 20) of: Met Ala His Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala Ala Gly Ala Ser Val Val Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr Leu Gin Gly He His Leu Lys Asn He Gin Ser Val Asn Val Arg Ser Pro Gly Pro His Cys Ala Gin Thr Glu Val He Ala Thr Leu Lys Asn Gly Lys Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Gin Lys He He Glu Lys He Leu Asn Lys Gly Ser Thr Asn encoded by the cDNA sequence (SEQ ID NO: 21) of: 1 CTCGCACAGC TTCCCGACGC GTCTGCTGAG CCCCATGGCC CACGCCACGC 51 TCTCCGCCGC CCCCAGCAAT CCCCGGCTCC TGCGGGTGGC GCTGCTGCTC 101 CTGCTCCTGG TGGCCGCCAG CCGGCGCGCA GCAGGAGCGT CCGTGGTCAC 151 TGAACTGCGC TGCCAGTGCT TGCAGACACT GCAGGGAATT CACCTCAAGA 201 ACATCCAAAG TGTGAATGTA AGGTCCCCCG GACCCCACTG CGCCCAAACC 251 GAAGTCATAG CCACACTCAA GAATGGGAAG AAAGCTTGTC TCAACCCCGC 301 ATCCCCCATG GTTCAGAAAA TCATCGAAAA GATACTGAAC AAGGGGAGCA 351 CCAACTGACA GGAGAGAAGT AAGAAGCTTA TCAGCGTATC ATTGACACTT 401 CCTGCAGGGT GGTCCCTGCC CTTACCAGAG CTGAAAATGA AAAAGAGAAC 451 AGCAGCTTTC TAGGGACAGC TGGAAAGGAC TTAATGTGTT TGACTATTTC 501 TTACGAGGGT TCTACTTATT TATGTATTTA TTTTTGAAAG CTTGTATTTT 551 AATATTTTAC ATGCTGTTAT TTAAAGATGT GAGTGTGTTT CATCAAACAT 601 AGCTCAGTCC TGATTATTTA ATTGGAATAT GATGGGTTTT AAATGTGTCA 651 TTAAACTAAT ATTTAGTGGG AGACCATAAT GTGTCAGCCA CCTTGATAAA 701 TGACAGGGTG GGGAACTGGA GGGTGGGGGG ATTGAAATGC AAGCAATTAG 751 TGGATCACTG TTAGGGTAAG GGAATGTATG TACACATCTA TTTTTTATAC 801 TTTTTTTTTA AAAAAAGAAT GTCAGTTGTT ATTTATTCAA ATTATCTCAC 851 ATTATGTGTT CAACATTTTT ATGCTGAAGT TTCCCTTAGA CATTTTATGT 901 CTTGCTTGTA GGGCATAATG CCTTGTTTAA TGTCCATTCT GCAGCGTTTC 951 TCTTTCCCTT GGAAAAGAGA ATTTATCATT ACTGTTAC which corresponds to the cDNA sequence and derived amino acid sequence gro-γ/MIP-2β (macrophage inflammatory protein 2-β). See Tekamp-Olson et al., J. Exp. Med. 172, 911-919 (1990). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 22) of: Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu He Ser Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu Arg Cys Gin Cys He Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe He Lys Glu Leu Arg Val He Glu Ser Gly Pro His Cys Ala Asn Thr Glu He He Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro Lys Glu Asn Trp Val Gin Arg Val Val Glu Lys Phe Leu Lys Arg Ala Glu encoded by the cDNA sequence (SEQ ID NO: 23) of: 1 ATGACTTCCA AGCTGGCCGT GGCTCTCTTG GCAGCCTTCC TGATTTCTGC 51 AGCTCTGTGT GAAGGTGCAG TTTTGCCAAG GAGTGCTAAA GAACTTAGAT 101 GTCAGTGCAT AAAGACATAC TCCAAACCTT TCCACCCCAA ATTTATCAAA 151 GAACTGAGAG TGATTGAGAG TGGACCACAC TGCGCCAACA CAGAAATTAT 201 TGTAAAGCTT TCTGATGGAA GAGAGCTCTG TCTGGACCCC AAGGAAAACT 251 GGGTGCAGAG GGTTGTGGAG AAGTTTTTGA AGAGGGCTGA G which corresponds to the cDNA sequence and derived amino acid sequence Interleukin-8/NAP-l (neutrophil activating protein-1). See Kunser et al., Kidney Int. 39, 1240-1248 (1991). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 24) of: Ala Gly Pro Ala Ala Ala Val Leu Arg Glu Lys Arg Cys Val Cys Leu Gin Thr Thr Gin Gly Val His Pro Lys Met He Ser Asn Leu Gin Val Phe Ala He Gly Pro Gin Cys Ser Lys Val Glu Val Val Ala Ser Leu Lys Asn Gly Lys Glu He Cys Leu Asp Pro Glu Ala Pro Phe Leu Lys Lys Val He Gin Lys He Leu Asp Gly Gly Asn Lys Glu Asn encoded by the cDNA sequence (SEQ ID NO: 25) of: 1 GTGTTGCGGGAACTGCGGTGCGTGTGTTTACAGACCACGCAGGGAGTTCA 51 TCCCAAAATGATCAGTAATCTGCAAGTGTTCGCCATAGGCCCACAGTGCT 101 CCAAGGTGGAAGTGGTAGCCTCCCTGAAGAACGGGAAGGAAATTTGTCTT 151 GATCCAGAAGCCCCTTTTCTAAAGAAAGTCATCCAGAAAATCCTCGACGG 201 CGGCAACAAAGAAAAC which corresponds to the cDNA sequence and derived amino acid sequence of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. See Walz et al., J. Exp. Med. 174, 1355-1362 (1991). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 26) of: Met Gin Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala Leu Cys Asn Gin Val Leu Ser Ala Pro Leu Ala Ala Asp Thr Pro Thr Ala Cys Cys Phe Ser Tyr Thr Ser Arg Gin He Pro Gin Asn Phe He Ala Asp Tyr Phe Glu Thr Ser Ser Gin Cys Ser Lys Pro Ser Val He Phe Leu Thr Lys Arg Gly Arg Gin Val Cys Ala Asp Pro Ser Glu Glu Trp Val Gin Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala encoded by the cDNA sequence (SEQ ID NO: 27) of: 1 GAATTCAAGG CCTGTCCTGG TTTGGTCCCA ATTTACCTTT ATCATCCATA 51 TTCACCCCCA CTGCTCTGCA GCTCCACTGA AGCACCCCCT CTTTCCTCTG 101 AGCCACAATG TCACACCCAG GACTCTGCCT CAGCTGGGCC TCCACTGCCC 151 ACCCATCTAT AGATGCCTAA ATCCCGGGCA GTTATCCAGA CACAACTAAA 201 GTTCCATCCC TTCCATGAAG CCTTCCCCAA CCCTCTGGTG GAAGGTCACT 251 TCTTCCTCAT GGGGTTCTGA GCTTTCATTT CTTTTTCTAC TAAGAGTTTT 301 ACAATTACCT GTTCATACAC TCTACCTGCC CCCATGAGAC CAGGGGCATC 351 TCAGAAACAA AGATCATTAA AACCAACTAA ATCTATTTCT CATTATAAAA 401 TGAGATATGC TGATTGATTG CAAAATAATA AAATAACAAA GTATGGAAAA 451 GAAAAAAAAA AGCATATAAT CTGGCTGAGA AGGTAGAGAC CCTTCCACAC 501 CACTGAAATT ATGTGTTGAA AAGAATAAGG AAAAAACTGC TTCAGTTTGG 551 CATTATTTAT GTAAGTATAG TATAGGATCC TTAAAATGGT TCAAAGAAAT 601 GGGAAATCAA GACTTCATTT TGGCAAAGCC ATTGAACAGA AACTGTAGCA 651 TATTTATCAG TAATTTCTTT CAGATTAAAC AACTGACAAC AACCCACTTT 701 TCAACCAGTG ATGTTGGAAA TGTTTTAAAA CAAAATTAGT TCATAAATTT 751 GTGGGTTGAC CAAGAAGGTA ATAAAGTCTC ACTAAATAAA ATGAGGAAAA 801 TTCAGAAAAA GAAAAAAATA AGAAAATAAA TCACCCATGG ATCTAAGCAC 851 TATTCATTCT TTAAGGCATG TATTTCCAAG CCTTTTAATT TTTTCATGCC 901 TAGAGTTGGC ATGGCATATA TATATCTTTA TACAATTCTT CAAATTTTAT 951 AGAATTTGTA TAATGTTTTA TCTTGCTTTT TTTTTAACCA CTGATGTTAT 1001 AAGCATATTT ATGCCACTTC ATTCACGTTA GAGACTTAAT AATAAAGGAT 1051 CTTGTGGATA ATTTATCATT CCCTGATAGA GAAAAATTTA GCTTTGCTTA 1101 TTTTAGAGTT ATAAATGATG CTGGGTCAGG TATCTTTATG TTTGAAGATG 1151 GCTCCATATT TGGGTTGTTT CCACAGAACT CTTTCCAGAA ATGCTTTTTC 1201 TAGGTTAATG GCTACACATA TTTCTAGGCA CCTGACATAC TGACACCCAC 1251 CTCTAAAGTA TTTTTATGAT CCACAACTAG CGTTTAACAC AGCGCCCCAG 1301 TCACTCCGAG ACTAATAAAT AGACAAATGA CTGAAACGTG ACCTCATGCT 1351 TTCTATTCCT CCAGCTTTCA TTGAGTTCCT TTCCTCTGGG AGGACTGGGG 1401 GTTGTCTAGC CCTCCACAGC ATCAGCCCAT TGACCCTATC CTTGTGGTTA 1451 TAGCAGCTGA GGAAGCAGAA TT * GCTCT GTGGGAAGGA ATGGGGCTGG 1501 AGAGTTCATG CATAGACCAA TTClTTTTTT TTTTTTTTTT TGAGATGGAG 1551 TTTCACTTTT GTTGCCCAGG CTGGAGTGCA ATGGCATGAT CTCAGCTCAC 1601 CACAGCCCCC ACCTCCTGGG TTCAAGCGAT TCTCCTGCCC TCAGCCTCCC 1651 GAGTAGCTGG GATTACAGGC ATGTGCCACC ACGCCTGACT ACTTTTGTAT 1701 TTTTAGTAGA GATGGAGTTT CTCTTTCTTG GTCAGGTTGG TCTCAAACTC 1751 CTGACCTCAG GTGATCTGCA GCCTCGGCCT CCAAAGTGTT GGGATTACAG 1801 GTGTGAGCGA CCATGCCTGG CTGCATAGAC CAGTTCTTAT GAGAAGGGAT 1851 CAACTAAGAA TAGCCTTGGG TTGACACACA CCCCTCTTCA CACTCACAGG 1901 AGAAACCCCA TGAAGCTAGA ACCAGTCATG AGTTGAGAGC TGAGAGTTAG 1951 AGAGTAGCTC AGAGATGCTA TTCTTGGATA TCCTGAGCCC CTGTGGTCAC 2001 CAGGGACCCT GAGTTGTGCA ACACTCAGCA TGACAGCATC ACTACACTTA 2051 AAAATTTCCC TCCTCACCCC CAGATTCCAT TTCCCCATCC GCCAGGGCTG 2101 CCTATAAAGA GGAGAGATGG CTTCAGACAT CAGAAGGACG CAGGCAGCAA 2151 AGAGTAGTCA GTCCCTTCTT GGCTCTGCTG ACACTCGAGC CCACATTCCA 2201 TCACCTGCTC CCAATCATGC AGGTCTCCAC TGCTGCCCTT GCCGTCCTCC 2251 TCTGCACCAT GGCTCTCTGC AACCAGGTCC TCTCTGCACC ACGTGAGTCC 2301 ATGTTGTTGT TGTGGGTATC ACCACTCTCT GGCCATGGTT AGACCACATC . 2351 AGTCTTTTTT TGTGGCGTGA GAGGCCCCGA AGAGAAAAGA AGGAAGTTCT 2401 TAAAGCGCTG CCAAACACCT TGGTCTTTTT CTTCACAACT TTTATTTTTA 2451 TCTCTAGAAG GGGTCTTAGC CCTCCTAGTC TCCAGGTATG AGAATCTAGG 2501 CAGGGGCAGG GGAGTTACAG TCCCTTGTAC AGATAGAAAA ACAGGGTTCA 2551 AAACGAATCA GTTTGCAAGA GGCAGAATCC AGGGCTGCTT ACTTCCCAGT 2601 GGGGTCTGTT CTTCACTCTC CAGCTCACCC TAGTCTCCCA GGAGCCCTGT 2651 CCCTTGGATG TCTTATGAGA GATGTCCAGG GCTTCTCTTG GGCTGGGGTA 2701 TGACTTCTTG AACCGACAAA ATTCCATGAA GAGAGCTAAG AGAACAGTCC 2751 ATTCAGGTAT CTGGATCACA TAGAGAAACA GAGAACCCAC TATGAAGAGT 2801 CAAGGGGAAA GAGGAATATA GACAGAAACA AAGAGACATT TCTCTGCAAA 2851 ACCCCCCAAA TGCCTTGCAG TCACTTGGTC TGAGCAAGCC TGCCCTCCTC 2901 AACCACTCAG GGATCAGAAG CTGCCTGGCC TTTTCTTCTG AGCTGTGACT 2951 TGGGCTTATT CTCTCCTTTC TCCGCAGTTG CTGCTGACAC GCCGACCGCC 3001 TGCTGCTTCA GCTACACCTC CCGACAGATT CCACAGAATT TCATAGCTGA 3051 CTACTTTGAG ACGAGCAGCC AGTGCTCCAA GCCCAGTGTC ATGTAAGTGC 3101 CAGTCTTCCT GCTCACCTCT AGGGAGGTAG GGAGTGTCAG GGTGGGGGCA 3151 GAAACAGGCC AGAAGGCCAT CCTGGAAAGG CCCAGCCTTC AGGAGCCTAT 3201 CGGGGATACA GGACGCAGGG CACTGAGGTG TGACCTGACT TGGGGCTGGA 3251 GTGAGGTGGG TGTTACAGAG TCAGGAAGGG CTGCCCCAGG CCAGAGGAAA 3301 GGGACAGGAA GAAGGAGGCA GCAGGACACT CTGAGGGCCC CCTTGCCTGG 3351 AGTCACTGAG AGAAGCTCTC TAGACGGAGA TAGGCAGGGG GCCCCTGAGA 3401 GAGGAGCAGG CCTTGAGCTG CCCAGGACAG AGAGCAGGAT GTCAGGGCCA 3451 TGGTGGGCCC AGGATTCCCC GGCTGGATTC CCCAGTGCTT AACTCTTCCT 3501 CCCTTCTCCA CAGCTTCCTA ACCAAGAGAG GCCGGCAGGT CTGTGCTGAC 3551 CCCAGTGAGG AGTGGGTCCA GAAATACGTC AGTGACCTGG AGCTGAGTGC 3601 CTGAGGGGTC CAGAAGCTTC GAGGCCCAGC GACCTCAGTG GGCCCAGTGG 3651 GGAGGAGCAG GAGCCTGAGC CTTGGGAACA TGCGTGTGAC CTCCACAGCT 3701 AΓCTCTTCTA TGGACTGGTT ATTGCCAAAC AGCCACACTG TGGGACTCTT 3751 CTTAACTTAA ATTTTAATTT ATTTATACTA TTTAGTTTTT ATAATTTATT 3801 TTTGATTTCA CAGTGTGTTT GTGATTGTTT GCTCTG 3AG TTCCCCCTGT 3851 CCCCTCCACC TTCCCTCACA GTGTGTCTGG TGACAACCGA GTGGCTGTCA 3901 TCGGCCTGTG TAGGCAGTCA TGGCACCAAA GCCACCAGAC TGACAAATGT 3951 GTATCAGATG CTTTTGTTCA GGGCTGTGAT CGGCCTGGG' AAATAATAAA 4001 GATGTTCTTT TAAACGGTAA ACCAGTATTG AGTTTGGTTT TGTTTTTCTG 4051 GCAAATCAAA ^TCACTGGTT AAGAGGAATC ATAGGCAAAG ATTAGGAAGA 4101 GGTGAAATGG AGGGAAATTG GGAGAGATGG GGAGCGCTGC GACAGAGTTA 4151 TCCACTTCAC AAAATTCTGG AACATTGAAA CTACGAATAT GTTATAACTC 4201 AAATCGTAAT ATGCACGCTC TAGGAGAATT AACTACTTGA ATGGCCAC( 4251 TTAAGCAGAG TATTCTGTAG GGCATATTCA TGATGAATCA AGCTCTTAAT 4301 AGCAATTATT TACATTGTTG AGGCTTACTC CTCCTACTGA GTGCTTTTTA 4351 TACATTGTTC ATTTAATCTT ACCAATGCAA AGTACAGCT TAGGTACTAT 4401 TAATACCTCC ACTTGACAGA AAAGTAACCC AGGGCTCAGA AAGGTTAGAC 4451 AACTTGGCTG AGGTTACACA GCACGTAAAC GGTCAATTGT GTTCCAAAAC 4501 TGGACTTTTA TTGAACTACA GACTATGCTG TTAACCATTG ACCAAGTTAT 4551 TTCCCAAAGT ATGACCCGCC TATACTCAAA TCTTACCCCA TTCTTTAACA 4601 GATGATACTT TATCCATTGC AACCACTTCC TGTCAGGATT CTGAGTTGAC 4651 ATAGAGTGTT TCAGCAGTGA TTATTTAAGC CAATTACATC AGGATCTTTA 4701 GGTGTAGACC TGGGAACTGA TATTTTTATC AAGCTCATGA GGTGTTCCAT 4751 AGCATGTTAA TGACTGAGAG CCACTGTCAA TAGAATTC which corresponds to the cDNA sequence and derived amino acid sequence MlP-lα (macrophage inflammatory protein 1-α). See Blum et al., DNA Cell Biol. 9, 589-602 (1990). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 28) of: Met Lys Leu Cys Val Thr Val Leu Ser Leu Leu Met Leu Val Ala Ala Phe Cys Ser Pro Ala Leu Ser Ala Pro Met Gly Ser Asp Pro Pro Thr Ala Cys Cys Phe Ser Tyr Thr Ala Arg Lys Leu Pro Arg Asn Phe Val Val Asp Tyr Tyr Glu Thr Ser Ser Leu Cys Ser Gin Pro Ala Val Val Phe Gin Thr Lys Arg Ser Lys Gin Val Cys Ala Asp Pro Ser Glu Ser Tip Val Gin Glu Tyr Val Tyr Asp Leu Glu Leu Asn encoded by the cDNA sequence (SEQ ID NO: 29) of: 1 TTCCCCCCCC CCCCCCCCCC CCCCGCCCGA GCACAGGACA CAGCTGGGTT 51 CTGAAGCTTC TGAGTTCTGC AGCCTCACCT CTGAGAAAAC CTCTTTTCCA 101 CCAATACCAT GAAGCTCTGC GTGACTGTCC TGTCTCTCCT CATGCTAGTA 151 GCTGCCTTCT GCTCTCCAGC GCTCTCAGCA CCAATGGGCT CAGACCCTCC 201 CACCGCCTGC TGCTTTTCTT ACACCGCGAG GAAGCTTCCT CGCAACTTTG 251 TGGTAGATTA CTATGAGACC AGCAGCCTCT GCTCCCAGCC AGCTGTGGTA 301 TTCCAAACCA AAAGAAGCAA GCAAGTCTGT GCTGATCCCA GTGAATCCTG 351 GGTCCAGGAG TACGTGTATG ACCTGGAACT GAACTGAGCT GCTCAGAGAC 401 AGGAAGTCTT CAGGGAAGGT CACCTGAGCC CGGATGCTTC TCCATGAGAC 451 ACATCTCCTC CATACTCAGG ACTCCTCTCC GCAGTTCCTG TCCCTTCTCT 501 TAATTTAATC TTTTTTATGT GCCGTGTTAT TGTATTAGGT GTCATTTCCA 551 TTATTTATAT TAGTTTAGCC AAAGGATAAG TGTCCTATGG GGATGGTCCA 601 CTGTCACTGT TTCTCTGCTG TTGCAAATAC ATGGATAACA CATTTGATTC 651 TGTGTGTTTT CCATAATAAA ACTTTAAAAT AAAATGCAGA CAGTTA which corresponds to the cDNA sequence and derived amino acid sequence MlP-lβ (macrophage inflammatory protein 1-β). See Lipes et al., Proc. Natl. Acad. Sci. U.S.A. 85, 9704-9708 (1988). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 30) of: Met Gin He He Thr Thr Ala Leu Val Cys Leu Leu Leu Ala Gly Met Trp Pro Glu Asp Val Asp Ser Lys Ser Met Gin Val Pro Phe Ser Arg Cys Cys Phe Ser Phe Ala Glu Gin Glu He Pro Leu Arg Ala He Leu Cys Tyr Arg Asn Thr Ser Ser He Cys Ser Asn Glu Gly Leu He Phe Lys Leu Lys Arg Gly Lys Glu Ala Cys Ala Leu Asp Thr Val Gly Trp Val Gin Arg His Arg Lys Met Leu Arg His Cys Pro Ser Lys Arg Lys encoded by the cDNA sequence (SEQ ID NO: 31) of: 1 ACCAGGCTCA TCAAAGCTGC TCCAGGAAGG CCCAAGCCAG ACCAGAAGAC 51 ATGCAGATCA TCACCACAGC CCTGGTGTGC TTGCTGCTAG CTGGGATGTG 101 GCCGGAAGAT GTGGACAGCA AGAGCATGCA GGTACCCTTC TCCAGATGTT 151 GCTTCTCATT TGCGGAGCAA GAGATTCCCC TGAGGGCAAT CCTGTGTTAC 201 AGAAATACCA GCTCCATCTG CTCCAATGAG GGCTTAATAT TCAAGCTGAA 251 GAGAGGCAAA GAGGCCTGCG CCTTGGACAC AGTTGGATGG GTTCAGAGGC 301 ACAGAAAAAT GCTGAGGCAC TGCCCGTCAA AAAGAAAATG AGCAGATTTC 351 TTTCCATTGT GGGCTCTGGA AACCACATGG CTTCACCTGT CCCCGAAACT 401 ACCAGCCCTA CACCATTCCT TCTGCCCTGC TTTTGCTAGG TCACAGAGGA 451 TCTGCTTGGT CTTGATAAGC TATGTTGTTG CACTTTAAAC ATTTAAATTA 501 TACAATCATC AACCCCCAAC which corresponds to the cDNA sequence and derived amino acid sequence human secreted protein (1-309). See Miller et al., J. Immunol. 143, 2907-2916 (1989). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 32) of: Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu He Ala Ala Thr Phe He Pro Gin Gly Lys Ala Gin Pro Asp Ala πe Asn Ala Pro Val Thr Cys Cys Tyr Asn Phe Thr Asn Arg Lys He Ser Val Gin Arg Leu Ala Ser Tyr Arg Arg He Thr r - - Ser Lys Cys Pro Lys Glu Ala Val He Phe Lys Thr He Val Ala Lys Glu He Ala A 'ro Lys Gin Lys Trp Val Gin Asp Ser Met Asp His Leu Asp Lys Gin Thr Gin Thr Pro Lys Thr encoded by the cDNA sequence (SEQ ID NO: 33) of: 1 CTAACCCAGA AACATCCAAT TCTCAAACTG AAGCTCGCAC TCTCGCCTCC 51 AGCATGAAAG TCTCTGCCGC CCTTCTGTGC CTGCTGCTCA TAGCAGCCAC 101 CTTCATTCCC CAAGGGCTCG CTCAGCCAGA TGCAATCAAT GCCCCAGTCA 151 CCTGCTGTTA TAACTTCACC AATAGGAAGA TCTCAGTGCA GAGGCTCGCG 201 AGCTATAGAA GAATCACCAG CAGCAAGTGT CCCAAAGAAG CTGTGATCTT 251 CAAGACCATT GTGGCCAAGG AGATCTGTGC TGACCCCAAG CAGAAGTGGG 301 TTCAGGATTC CATGGACCAC CTGGACAAGC AAACCCAAAC TCCGAAGACT 351 TGAACACTCA CTCCACAACC CAAGAATCTG CAGCTAACTT ATTTTCCCCT 401 AGCTTTCCCC AGACACCCTG TTTTATTTTA TTATAATGAA TTTTGTTTGT 451 TGATGTGAAA CATTATGCCT TAAGTAATGT TAATTCTTAT TTAAGTTATT 501 GATGTTTTAA GTTTATCTTT CATGGTACTA GTGTTTTTTA GATACAGAGA 551 CTTGGGGAAA TTGCTTTTCC TCTTGAACCA CAGTTCTACC CCTGGGATGT 601 TTTGAGGGTC TTTGCAAGAA TCATTAATAC AAAGAATTTT TTTTAACATT 651 CCAATGCATT GCTAAAATAT TATTGTGGAA ATGAATATTT TGTAACTATT 701 ACACCAAATA AATATATTTT TGTAC which corresponds to the cDNA sequence and derived amino acid sequence monocyte chemoattractant protein 1 (MCP-1). See Yoshimura et al., FEBS Lett. 244, 487-493 (1989). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 34) of: Met Lys Ala Ser Ala Ala Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala Phe Ser Pro Gin Gly Leu Ala Gin Pro Val Gly He Asn Thr Ser Thr Thr Cys Cys Tyr Arg Phe He Asn Lys Lys He Pro Lys Gin Arg Leu Glu Ser Tyr Arg Arg Thr Thr Ser Ser His Cys Pro Arg Glu Ala Val He Phe Lys Thr Lys Leu Asp Lys Glu He Cys Ala Asp Pro Thr Gin Lys Trp Val Gin Asp Phe Met Lys His Leu Asp Lys Lys Thr Gin Thr Pro Lys Leu encoded by the cDNA sequence (SEQ ID NO: 35) of: 1 AGCAGAGGGG CTGAGACCAA ACCAGAAACC TCCAATTCTC ATGTGGAAGC 51 CCATGCCCTC ACCCTCCAAC ATGAAAGCCT CTGCAGCACT TCTGTGTCTG 101 CTGCTCACAG CAGCTGCTTT CAGCCCCCAG GGGCTTGCTC AGCCAGTTGG 151 GATTAATACT TCAACTACCT GCTGCTACAG ATTTATCAAT AAGAAAATCC 201 CTAAGCAGAG GCTGGAGAGC TACAGAAGGA CCACCAGTAG CCACTGTCCC 251 CGGGAAGCTG TAATCTTCAA GACCAAACTG GACAAGGAGA TCTGTGCTGA 301 CCCCACACAG AAGTGGGTCC AGGACTTTAT GAAGCACCTG GACAAGAAAA 351 CCCAAACTCC AAAGCTTTGA ACATTCATGA CTGAACTAAA AACAAGCCAT 401 GACTTGAGAA ACAAATAATT TGTATACCCT GTCCTTTCTC AGAGTGGTTC 451 TGAGATTATT TTAATCTAAT TCTAAGGAAT ATGAGCTTTA TGTAATAATG 501 TGAATCATGG TTTTTCTTAG TAGATTTTAA AAGTTATTAA TATTTTAATT 551 TAATCTTCCA TGGATTTTGG TGGGTTTTGA ACATAAAGCC TTGGATGTAT 601 ATGTCATCTC AGTGCTGTAA AAACTGTGGG ATGCTCCTCC CTTCTCTACC 651 TCATGGGGGT ATTGTATAAG TCCTTGCAAG AATCAGTGCA AAGATTTGCT 701 TTAATTGTTA AGATATGATG TCCCTATGGA AGCATATTGT TATTATATAA 751 TTACATATTT GCATATGTAT GACTCCCAAA TTTTCACATA AAATAGATTT 801 TTGTAAAAAA which corresponds to the cDNA sequence and derived amino acid sequence monocyte chemoattractant protein 3 (MCP-3). See: Structural and Functional Identification of Two Human, Tumor-derived Monocyte Chemotactic Proteins (MCP-2 and MCP-3) Belonging to the Chemokine Family. Jo Van Damme, Paul Proost, Jean-Pierre Lenaerts, and Ghislain Opdenakker. J. Exp. Med. 176: 59-65, 1992. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 36) of: Met Lys Val Ser Ala Ala Arg Leu Ala Val He Leu He Ala Thr Ala Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro Cys Cys Phe Ala Tyr He Ala Arg Pro Leu Pro Arg Ala His He Lys Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe Val Thr Arg Lys Asn Arg Gin Val Cys Ala Asn Pro Glu Lys Lys Trp Val Arg Glu Tyr He Asn Ser Leu Glu Met Ser encoded by the cDNA sequence (SEQ ID NO: 37) of: 1 CCTCCGACAG CCTCTCCACA GGTACCATGA AGGTCTCCGC GGCACGCCTC 51 GCTGTCATCC TCATTGCTAC TGCCCTCTGC GCTCCTGCAT CTGCCTCCCC 101 ATATTCCTCG GACACCACAC CCTGCTGCTT TGCCTACATT GCCCGCCCAC 151 TGCCCCGTGC CCACATCAAG GAGTATTTCT ACACCAGTGG CAAGTGCTCC 201 AACCCAGCAG TCGTCTTTGT CACCCGAAAG AACCGCCAAG TGTGTGCCAA 251 CCCAGAGAAG AAATGGGTTC GGGAGTACAT CAACTCTTTG GAGATGAGCT 301 AGGATGGAGA GTCCTTGAAC CTGAACTTAC ACAAATTTGC CTGTTTCTGC 351 TTGCTCTTGT CCTAGCTTGG GAGGCTTCCC CTCACTATCC TACCCCACCC 401 GCTCCTTGAA GGGCCCAGAT TCTGACCACG ACGAGCAGCA GTTACAAAAA 451 CCTTCCCCAG GCTGGACGTG GTGGCTCAGC CTTGTAATCC CAGCACTTTG 501 GGAGGCCAAG GTGGGTGGAT CACTTGAGGT CAGGAGTTCG AGACAGCCTG 551 GCCAACATGA TGAAACCCCA TGTGTACTAA AAATACAAAA AATTAGCCGG 601 GCGTGGTAGC GGGCGCCTGT AGTCCCAGCT ACTCGGGAGG CTGAGGCAGG 651 AGAATGGCGT GAACCCGGGA GCGGAGCTTG CAGTGAGCCG AGATCGCGCC 701 ACTGCACTCC AGCCTGGGCG ACAGAGCGAG ACTCCGTCTC AAAAAAAAAA 751 AAAAAAAAAA AAAAAATACA AAAATTAGCC GCGTGGTGGC CCACGCCTGT 801 AATCCCAGCT ACTCGGGAGG CTAAGGCAGG AAAATTGTTT GAACCCAGGA 851 GGTGGAGGCT GCAGTGAGCT GAGATTGTGC CACTTCACTC CAGCCTGGGT 901 GACAAAGTGA GACTCCGTCA CAACAACAAC AACAAAAAGC TTCCCCAACT 951 AAAGCCTAGA AGAGCTTCTG AGGCGCTGCT TTGTCAAAAG GAAGTCTCTA 1001 GGTTCTGAGC TCTGGCTTTG CCTTGGCTTT GCAAGGGCTC TGTGACAAGG 1051 AAGGAAGTCA GCATGCCTCT AGAGGCAAGG AAGGGAGGAA CACTGCACTC 1101 TTAAGCTTCC GCCGTCTCAA CCCCTCACAG GAGCTTACTG GCAAACATGA 1151 AAAATCGGGG which corresponds to the cDNA sequence and derived amino acid sequence Human T cell-specific protein (RANTES). See Schall et al., J. Immunol. 141, 1018-1025 (1988). In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 38) of: Met Arg He Ser Ala Thr Leu Leu Cys Leu Leu Leu He Ala Ala Ala Phe Ser He Gin Val Trp Ala Gin Pro Asp Gly Pro Asn Ala Ser Thr Cys Cys Tyr Val Lys Lys Gin Lys He Pro Lys Arg Asn Leu Lys Ser Tyr Arg Arg He Thr Ser Ser Arg Cys Pro Trp Glu Ala Val He Phe Lys Thr Lys Lys Gly Met Glu Val Cys Arg Glu Ala His Gin Lys Trp Val Glu Glu Ala He Ala Tyr Leu Asp Met Lys Thr Pro Thr Pro Lys Pro encoded by the cDNA sequence (SEQ ID NO: 39) of: 1 ACTGAAGCCA GCTCTCTCAC TCTCTTTCTC CACCATGAGG ATCTCTGCCA 51 CGCTTCTGTG CCTGCTGCTC ATAGCCGCTG CTTTCAGCAT CCAAGTGTGG 101 GCCCAACCAG ATGGGCCCAA TGCATCCACA TGCTGCTATG TCAAGAAACA 151 AAAGATCCCC AAGAGGAATC TCAAGAGCTA CAGAAGGATC ACCAGTAGTC 201 GGTGTCCCTG GGAAGCTGTT ATCTTCAAGA CAAAGAAGGG CATGGAAGTC 251 TGTCGTGAAG CCCATCAGAA GTGGGTCGAG GAGGCTATAG CATACTTAGA 301 CATGAAAACC CCAACTCCAA AGCCTTGAAG AAATGTGCCT GAACAGAAAC 351 CAACCTAGGA GCCAAGAAGC AAAAATTCCT CACCGCTGTT CTTTCTGAGA 401 ACTGTTGATG AAATGTGTTG ATCACGGTCC TAAGGGATAG GAGCTGTCTG 451 TAGGAATGTG AAACAGTCAC GCCTAAGGAA TGGTCTTTAA GTTATTAATA 501 TTTTTATTTA ATTAGCCATG TACTTTGGTG TGATTTGAAT GTAAAGCTCT 551 GGAGACCTCA TGTCACTTTA ACATTGTGTT AGCTGCAGAA TTC which corresponds to the cDNA sequence and derived amino acid sequence human fie (growth factor-activated gene). See Heinrich et al., Molecular and Cellular Biology 13: 2020-2030, 1993. In another aspect, the present invention provides a heparanase having the amino acid sequence (SEQ ID NO: 40) of: Asp Ser Val Ser He Phe He Thr Cys Cys Phe Asn Val He Asn Arg Lys He Pro He Gin Arg Leu Glu Ser Tyr Thr Arg He Thr Asn He Gin Cys Pro Lys Glu Ala Val He Phe Lys Thr Gly Lys Glu Val Cys Ala Asp Pro Lys Glu Arg Trp Val Arg Asp Ser Met Lys His Lys Asp Gin He Phe Gin Asn Leu Lys Pro which corresponds to the cDNA sequence and derived amino acid sequence monocyte chemoattractant protein 2 (MCP-2). See VanDamme et al., J. Exp. Med. 176: 59 - 65, 1992. The purified heparanase of the present invention, allows for the convenient selection of compounds having anti-heparanase activity (AHA compounds), i.e. inhibitors of heparanase activity (IHA), by measuring inhibition of heparanase activity. Inhibition of heparanase activity can be measured utilizing in vivo radiolabeled heparan sulfate/heparin. This ligand is radiolabeled to high specific activity by intraperitoneal injection of 0.5mCi of S-35 sulfate into C57 mice bearing a 1-2 cm basement membrane tumor (EHS; Engelbreth, Holm, Swarm tumor). The tumor is harvested after 16 hours and the heparan sulfate proteoglycan extracted in 4 volumes of 6M urea, 20mM Tris pH 6.8, protease inhibitors, 0.15M NaCl and 0.5% triton X- 100. The urea extract is chromatographed on an anion exchange column and the proteoglycan is eluted in a linear gradient of NaCl. The radiolabeled proteoglycan is exchanged into a solution of 4.0M guanidine-HCl, 20mM Tris pH 7.4 and applied to a size exclusion column. The proteoglycan peak is pooled and exchanged into 0.15mM NaCl and 20mM Tris pH7.4. Purified, radiolabeled proteoglycan is coupled to commercially available agarose support. A quantitative assay of heparanase activity is constructed with the radiolabeled ligand in a multi- well format. Briefly, known quantities of recombinant heparanase are added to a multi-well plate containing equal amounts of radiolabeled ligand in each well. Enzyme-ligand interaction proceeds overnight and the ligand-agarose complex is recovered by centrifugation. Radioactivity in the liquid phase is determined by scintillation counting and is the measure of enzyme activity. Potential enzyme inhibitors can be evaluated by adding the compound to the solution phase or alternatively adding the assay components to multi-well plates containing preweighed amounts of test compound. In addition, the purified heparanase of the subject invention can be used for therapeutic wound healing or can be immobilized onto filters and used to degrade heparin from the blood of patients post-surgery. Wound treatment can be achieved by administration to an afflicted individual an effective amount of a pharmaceutical composition comprising the purified heparanase in combination with a pharmaceutically acceptable, preferably slow releasing, carrier. See. e.g. PCT US90/04772, incorporated herein by reference. Immobilization onto filters can be achieved by the methods well known in the art including those disclosed by Langer et al. in Biomaterials: Inter-facial Phenomenon and Applications, eds. Cooper et al, pp 493-509, 1982 and those described in U.S. Patent No. 4,373,023, 4,863,611 and 5,211,850 (all incorporated herein by reference). The purified heparanase of the subject invention can be prepared by the method described in procedure A or procedure B, but preferably procedure A. PROCEDURE A Reverse transcription of the mRNA from activated human leukocyte-derived cells [preferably lymphocytes, neutrophils, platelets, Jurkitt lymphoma cells, Dami cells (Greenberg et al., Blood 72:1968-1977, (1988)] is used to prepare the cDNA for the desired heparanase enzyme (preferably SEQ. ID. NO: 1; optionally SEO ID. NO: 3, SEQ. ID. NO: 5, SEQ. ID. NO: 7; SEQ. ID. NO: 13, SEQ. JD. NO: 15, SEQ. ID. NO: 17, SEQ. ID. NO: 19, SEQ. JD. NO: 21, SEQ. ID. NO: 23, SEQ. ID. NO: 25, SEQ. ID. NO: 27, SEQ. JD. NO: 29; SEQ. JD. NO: 31, SEQ. ID. NO: 33 or SEQ. ID. NO: 35), employing standard PCR cloning techniques (described in Sambrook et al., in: Molecular Cloning, A Laboratory Manual. Second Edition, 1989. Cold Spring Harbor Press). The cDNA encoding the heparanase enzyme is cloned into Xbal/BamHl sites in the commercially available baculovirus vector pVL 1392 (Pharmingen; San Diego, CA). High titer infectious virus is selected for use in infecting sf9 insect cells (Luckow and Summers, Bio/Technology. 6,47 1988). Serum-free medium conditioned by infected sf9 cells is collected after 72 hours. This media is the starting material for purification of recombinant heparanase. Serum-free conditioned media is adjusted to contain 20mM Sodium Acetate, pH 5.0, 0.15M NaCl, ImM reduced glutathione (GSH), ImM dithiothreitol (DTT) and lOmM beta-octylglucoside. Medium is applied to a column of cation-exchange resin (Pharmacia) and eluted from the column in a linear gradient of NaCl. Fractions containing heparanase are pooled and diluted to a final salt concentration of 0.15M NaCl. To this solution is added 20mM Tris and the pH adjusted to 7.0. The solution is applied to a column of heparin-Sepharose (Pharmacia) and eluted with a linear salt gradient buffered to pH 5.0 with 20mM Sodium Acetate. Heparanase is concentrated to 0.5mg/ml in an Amicon concentrator fitted with a YM-2 membrane and stored at -80 degrees. For optimal activity (greater than 50 units heparanase activity per wg protein) incubation in the presence of transglutaminase, under reducing conditions, in accordance with the procedure in Example 2, Part C. PROCEDURE B This procedure describes the purification to homogeneity of heparanase (SEQ. ID. NO: 1) from human blood cells or cell lines (such as platelets) under reducing conditions which allow for the occurrence of post-translational modifications that increase the specific activity of heparanase and make it suitable for use in the above described screening assay. The cells are treated with a suitable activator (such as, but not limited to, thrombin or histamine) which allows for the release of enzymes and cytokines from the cell. Reducing agents are added to the supernatant from the activated cells. Suitable reducing agents include dithiothreitol (DTT), dithioerythritol (DTE), reduced glutathione (GSH), and β-mercaptoethanol. The reduced, activated supernatant is chromatographed on a column of immobilized heparin or heparan sulfate under reducing conditions at pH 5, using a salt gradient (such as NaCl, KC1, or other salt) to elute the bound proteins. Fractions containing heparanase activity are pooled and exchanged into any buffer appropriate for the pH of 6.8 and containing 0.15 M NaCl, reducing agents, and non-ionic detergent. This is passed over any suitable anion-exchange column (bed volume of 5 ml or less). The unbound material from this column is adjusted to pH 5 with acid, and is loaded onto any suitable cation-exchange column (bed volume of 5 ml or less), equilibrated in a suitable pH 5 buffer containing 0.15 M NaCl, reducing agents, and non-ionic detergents. The bound protein is eluted from the column with a salt gradient, and the fractions containing heparanase activity are pooled and size fractionated to below 30,000 daltons with 30 K-cut-off membranes. The protein below 30,000 daltons is concentrated by either heparin-sepharose chromatography or by centrifugation through 5 K-cut-off membranes. The present invention is seen more fully by the examples set forth below. Example 1: Use of Heparanase as a screen for AHA compounds. 1. Heparan sulfate, metabolically labeled (S-35) to a high-specific activity- as described above for the EHS tumor, prepared by papain digestion of chromatographically purified heparan sulfate proteoglycan is coupled to cyanogen bromide activated Sepharose-6B (Pharmacia) according to manufacturer's instructions. 2. 35 S-Heparan sulfate-Sepharose 6B is resuspended in: 0.15 M NaCl, 0.03% human serum albumin, 10 μM MgCl 2 , 10 μM CaCl 2 , antiproteolytic agents (1 μg/ml leupeptin, 2 μg/ml antipain, 10 μg/ml benzamidine, 10 units/ml aprotinin, 1 μg/ml chymostatin, and 1 μg/ml pepstatin), and 0.05 M Na acetate, pH 5.6 and 5,000 cpm, in a total volume of 200 μl, are aliquoted into each well of a 96 well plate. To each well is added 5 units of activated heparanase and the digestion allowed to proceed overnight at 37 degrees. 3. Separation of digested product is accomplished by centrifugation of the 96 well plate. The supernatant, containing cleaved heparan sulfate is decanted and quantitated by scintillation counting. 4. Inhibitors of heparanase activity can be introduced into the liquid-phase of the assay. 5. A potential inhibitor of heparanase activity would be identified by its ability to reduce the amount of radiolabeled heparan sulfate released into the supernatant by 50% at a concentration of 1 μM or less. Example 2: The preparation of heparanase under reducing conditions as outlined in Procedure B. Part A: Platelet-rich plasma (10 9 platelets/ml; 1800 r. l) is obtained from healthy, ---formed volunteers by plasmapheresis. The plasma is removed from the platelets by centrifugation (Heldin, et al, Exp. Cell Res. 109: 429-437, 1977). Platelets suspended in phosphate buffered saline (PBS; 0.1 original volume) are then stimulated with 1 U/ml thrombin for 5 min at 37°C. This concentration of thrombin was reported to release 100% of the heparanase activity from platelets (Oldberg, et al, Biochemistry 19: 755-5762, 1980). Following activation, the thrombin is inactivated by the addition of 100 mM phenylmethylsulfonylfluoride (PMSF), and the platelets are centrifuged at 2000 x g for 30 min at 4°C. The supernatant is stored at -80°C until used for the chromatographic purification of heparanase (Part B). Part B: Chromatographic purification of heparanase. 1. Heparin-Sepharose Chromatography. Activated platelet supernatants are pooled and adjusted to contain 1 mM GSH and 1 mM DTT. This pool is loaded (2.5 ml min) onto a column of heparin-sepharose (2.6 x 7.5 cm, 40 ml) equilibrated in 1 mM GSH, 1 mM DTT, 150 mM NaCl, 10 mM NaPO 4 , pH 7.4. After loading the sample, the column is washed with 200 ml of 0.15 M NaCl, 1 mM GSH, 1 mM DTT, 10 mM Na acetate, pH 5, foUowed by 60 ml of 0.35 M NaCl, 1 mM DTT, 1 mM GSH, 10 mM Na acetate, pH 5. The column is then eluted with a 160 ml linear gradient between 0.35 M NaCl and 1.5 M NaCl in the same buffer. Aliquots of each fraction are used for determination of heparanase activity by the "Purification Assay" described later. 2. Anion-exchange chromatography (For example, DEAE-Sephacel, Pharmacia). The 0.9 M - 1.15 M NaCl fractions from the heparin-sepharose column are concentrated using a stirred cell fitted with a PM-10 membrane, and the buffer is exchanged to 0.15 M NaCl, 1 mM DTT, 1 mM GSH, 10 mM β-octylglucoside, 10 mM sodium phosphate, pH 6.8 (8 ml). This sample is loaded onto a 5 ml column of DEAE-Sephacel equilibrated in the same buffer. After loading, the column is washed to baseline absorbance (280 nm) with the equilibration buffer. The flow- through and wash with equilibration buffer are collected as one pool. The column is then eluted with 10 ml of 0.15 M NaCl, 10 mM β-octylglucoside, 1 mM GSH, 1 mM DTT, 10 mM Na acetate, pH 5, followed by 10 ml of 1.5 M NaCl, 10 mM β-octylglucoside, 1 mM GSH, 1 mM DTT, 10 mM Na acetate, pH 5. Aliquots of each pool are used for determination of heparanase activity by the "Purification Assay". 3. Cation Exchange. The unbound sample from the DEAE-Sephacel column is adjusted to pH 5 with glacial acetic acid and loaded onto a cation exchange column (Poros HS/F, 4.6 mm x 50 mm; PerSeptive Biosystems), pre-equilibrated with 0.15 M NaCl, 1 mM DTT, 1 mM GSH, 10 mM β-octylglucoside, 10 mM Na acetate, pH 5. The flow rate is 3.0 ml/min and 3 ml fractions are collected. After washing the column with 35 ml of equilibration buffer, the column is developed with a 55 ml linear gradient between 0.15 M and 1.5 M NaCl in the same buffer. 10 μl aliquots of the fractions are used for determination of heparanase activity by the "Purification Assay". 4. Size fractionation to < 30 kD and concentration on immobilized heparin (Hi-trap heparin-sepharose, Pharmacia). The activity from the Poros HS/F column is size fractionated by centrifuging through 30,000 molecular weight cut-off filters (Millipore ultrafree-MC 30,000 NMWL filter units). The < 30 kD pool is diluted to contain 0.15 M NaCl, and is loaded onto a 1 ml Hi-trap heparin column, pre-equilibrated with 0.15 M NaCl, 1 mM DTT, 1 mM GSH, 10 mM Na acetate, pH 5. The column is eluted with 1.2 M NaCl in the same buffer and the single eluted peak contains the heparanase activity. Part C: Properties of the purified heparanase. The final yield of heparanase protein from 1850 ml platelet-rich plasma was 2.7 mg. Protein concentration was determined by the method of Lowry J. Biol. Chem. 193: 265-275, 1951), or if more precise determinations were required, by amino acid analysis on an amino acid analyzer (Beckman 6300). The overall recovery of activity was 8%, with a 4150-fold purification. The preparation was judged to be homogeneous by the presence of a single band of 9000 daltons on an 18% silver-stained SDS-polyacrylamide gel, run according to the method of Laemmli (Nαtκre 227: 680-685, 1970). The pH optimum of the purified heparanase was determined by conducting the "Purification assay" activity between pH 3.5 and 8.0, using a citrate buffer (pH 3.5 - 6.0), citrate-phosphate buffer (pH 6.5 - 7.0), and phosphate buffer (pH 7.5 - 8.). Heparanase was active between pH 5.0 and 8.0, with the optimum pH at 5.8. N-terminal amino acid sequencing of heparanase produced by this procedure was performed using a gas/liquid phase Protein Sequencer (Applied Biosystems Inc. Model 470). Phenylthiodantoin amino acids were resolved and quantitated by an on-line HPLC system (Model 120, Applied Biosystems Inc.) with data analysis on a Nelson Analytical System. N- terminal amino acid sequences of the heparanase produced in this example were 85 % SEQ. ID. NO: 9 (namely: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala 1 5 10 15 Glu Leu Arg), which is identical to CTAP-HI, and 15% SEQ. ID. NO: 10 (namely: Ser Ser Thr Lys Gly Gin Thr Lys Arg Asn Leu Ala Lys Gly Lys Glu), 1 5 10 15 which is the precursor form, platelet basic protein. Interestingly, the N-terminal sequence of commercial β-thromboglobulin (namely, Calbiochem (Cat. # 605165), Celsus Laboratories (Cat. # 41705), and Haematologic Technologies (Cat. # HBTG-0210), which has low levels of heparanase activity, was 100% SEQ. ID. NO: 11 (namely: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala Glu), 1 _m_5 10 .15 indicating that e commercial preparatio. is actually CTAP-πi and not β-thromboglobulin. Chromatofocusing of the heparanase produced by this procedure results in two peaks of differing isoelectric points. To perform the chromatofocusing, heparanase is dissolved in 0.025 M imidazole, pH 7.3. The sample is loaded onto a 0.5 x 20 cm column of Polybuffer Exchanger 94 (Pharmacia), equilibrated with 0.025 M imidazole, pH 7.3. Immediately after sample loading, Polybuffer 74 (Pharmacia; 1:8, pH 4) is pumped onto the column at 0.5 ml/min. 2 ml fractions are collected, and the pH of each fraction is determined by a narrow range (pH 4- 7) pH paper. Aliquots of each fraction are used to determine heparanase activity by the "Purification Assay." All of the activity is associated with an absorbance (280 nm) peak that eluted at pH 4.8 to 5.1, representing approximately 10% of total protein, while 90% of the protein is eluted at pH 7.3 and is inactive. Aliquots of each protein peak are separated from the ampholytes by C reverse phase chromatography. The peak that eluted from the chromato- focusing column at pH 7.3 has N-terminal sequences for platelet basic protein and the processed form, CTAP-HI. The peak that is eluted from the chromatofocusing column at pH 4.8 - 5.1 also contains the sequences of platelet basic protein and the processed form, CTAP-IQ. All of the platelet basic protein processed forms have pi's that are calculated and reported to be greater than 7.6. Thus, the heparanase activity resides in the platelet basic protein and/or the processed form, CTAP-IH that is modified such that the pi is lowered to 4.8 - 5.1. Heparanase obtained after rltromatofocusing exhibited a specific activity of 80 unitr g protein, using the "Purification Assay." This represents a 1000-fold increase in the specific activity compared to the commercial protein (β-thromboglobulin; 0.075 units/μg protein). The modification that may be responsible for the lower isoelectric point of active heparanase is ADP-ribosylation. ADP-ribosylation (Adenine diphosphate-ribosylation) is a post¬ translational modification of proteins or DΝA in which the ADP-ribose group of NAD (Nicotinamide adenine dinucleotide) is enzymatically transfeπed to proteins or DNA. Since this modification adds two negatively charged phosphate groups to a molecule, it would result in a lower isoelectric point. Activated platelet supernatants were incubated in 1 mM DTT, 2 mM MgCl 2 , 100 mM HEPES, pH 7.4, and 0.5 μM [ 32 P]NAD (Specific activity = 1000 Ci/mmol). The labeled proteins were separated by SDS-polyacrylamide gel electrophoresis on an 18% gel, transferred to PVDF (polyvinylidene difluoride) membrane, and exposed to X-ray film. The autoradiogram demonstrates the incorporation of [ 32 P] into a protein of 8000 daltons. The PVDF membrane was immunoblotted with the anti-Peptide C antisera (1:1500 in PBS containing 5% dry milk, 0.05% Tween-20, 0.15 M NaCl, 20 mM Tris, pH 7.4, 2 hours at room temperature, followed by incubation with peroxidase-labeled goat anti-chicken IgG (1:500 in above buffer, 1 hour room temperature), and reacted with a peroxidase substrate. The immunoblot revealed that the 8000 dalton that was labeled with [ 32 P] was CTAP-ϋl/heparanase. The addition of 200 μM sodium nitroprusside, a spontaneous releaser of nitric oxide, to the ADP-ribosylation reaction resulted in 5-fold more incorporation of [ 32 P] label into CTAP- ϋl/heparanase, suggesting that this modification can be regulated in vivo by nitric oxide. Finally, in an analgous manner to that of glyceraldehyde-3-phosphate dehydrogenase, another platelet ADP-ribosylated glycolytic enzyme (Zhang and Snyder, Proc. Natl. Acad. Sci. USA 89: 9382-9385), it was determined that CTAP-m/heparanase has an auto-ADP-ribosylation activity, since the [ 32 P] -ADP-ribosylation of CTAP-HI/heparanase occurs in reactions where the only protein present is commercial CTAP-HI or purified heparanase. Other chemokine family members tested, which includes IP-1-, IL-8, gro-α, and MCAF, also have auto-ADP-ribosylation activity. It is contemplated that the high specific activity of CTAP-HI/heparanase is a consequence of ADP-ribosylation of the enzyme in the presence of nitric oxide. It is further contemplated that the action of transglutaminase on the ADP-ribosylated enzyme will lead to further increase in the specific activity. An amino acid composition of the heparanase produced in Example 2 gave the expected amino acid composition for CTAP-HI and N-terminal sequencing revealed sequences for platelet basic protein and the processed form, CTAP-πi , confirming that the heparanase activity is contained in this set of processed proteins and is not due to a minor contaminant. The presence of heparanase activity in three commercial sources of β-thromboglobulin also confirms this conclusion. In addition, polyclonal antibodies to β-thromboglobulin were found to precipitate 30 - 70% of the heparanase activity in three separate experiments, providing additional confirmation. The activation of heparanase with transglutaminase (prepared in accordance with Example 2, Part B) results in a substantial (about 13-fold) increase in the specific activity of the enzyme. The heparanase (2 wl at 56 nM) obtained by Example 2, Part B is treated with either transglutaminase from guinea pig liver (4 mU; Sigma) or with Factor XIH (1 μg; Celsus Laboratories, Inc.), the blood coagulation factor that is activated by treatment with 5 units of thrombin at 37 degrees for 30 minutes. Heparanase is activated by incubation of either 2mU liver transglutaminase or 5 units of activated Factor XIH in the presence of 0.1 M NaAcetate buffer at pH 6.0 containing ImM reduced glutathione and ImM CaCl for 35 minutes at 37 degrees. Treatment of heparanase with either type of transglutaminase results in a substantial increase in the specific activity of the heparanase. The high degree of sequence identity between CTAP-HI ai . , lr-terleukin-8, a CXC chemokine family member, assures that an essentially identical folding pattern will be shared by the two proteins. Since the 3-dimensional structure of Interleukin-8 is known (Clore, et al., Biochemistry 29: 1689-1696,1990; Baldwin, et al, J. Biol. Chem. 265: 6851-6853), one can model the same for CTAP-HI. Such a model can serve to direct r arch into rationally designed IHA and to help explain the action of transglutaminase in activating the CTAP-HI. Part D: Purification Assay for Heparanase Activity Heparanase activity from platelets or column fractions is detected by its ability to digest the > 70 kD S-HSPG to produce lower molecular weight products. Each digest contains 10 μl sample, 35 S-HSPG (2000 cpm), 0.15 M NaCl, 0.03% human serum albumin, 10 μM MgCl 2 , 10 μM CaCl 2 , antiproteolytic agents (1 μg/ml leupeptin, 2 μg/ml antipain, 10 μg/ml benzamidine, 10 units/ml aprotinin, 1 μg ml chymostatin, and 1 μg/ml pepstatin), and 0.05 M Na acetate, pH 5.6 in a total volume of 300 μl. Digests are carried out for 3 to 21 h. The presence of lower molecular weight radiolabeled products is detected by centrifugation through 30,000 MW-cutoff filters. The digests containing 2000 cpm of 35 S-HSPG (> 70 K) are centrifuged through 30,000 molecular weight cut-off filters (MiUipore Ultrafree-MC 30,000 NMWL filter units). 35 S-HSPG degradation is evident by the presence of radioactivity in the filtrate that passed through the 30 K membrane; this heparanase activity is expressed as the % of total cpm < 30 K for a given digest. Analysis of heparan sulfate degradation by this method is quick and reproducible. 1 unit of heparanase activity is defined as 1% cpm < 30 K per h. For pH optimum determination, the 0.1 M Na acetate buffer is replaced by 50 mM citrate, citrate-phosphate, or phosphate buffer at varying pH's. For samples from chromatographic steps performed under reducing conditions (1 mM GSH, 1 mM DTT), the concentration of a thiol oxidant (diamide) needed for optimum activity is determined. This concentration (100 μM diamide) is added to all assay tubes when reduced samples are assayed. Preparation of 35 S-HSPG (>70 K) for use in the 'Purification Assay." 35 S-HSPG (>70 K) is prepared from mice bearing a basement membrane tumor that overproduces HSPG (EHS tumor), using modifications of the method of Ledbetter, et. al., 1987. Briefly, the radiolabeled HSPG was prepared by injecting C57BL mice bearing the EHS tumor (Orkin, et.al., 1977) with sodium [ 35 S]sulfate (0.5 mCi/mouse) 18 h before harvesting the tumor. The HSPG is extracted from the weighed tumor with 6 volumes (w/v) of Buffer A (3.4 M NaCl, 0.1 M 6-aminohexanoic acid, 0.04 M EDTA, 0.008 M N-ethylmaleimide, 0.002 M PMSF, and 0.05 M Tris-HCl, pH 6.8), by homogenization with a Polytron for 30 s, followed by stirring at 4°C for 1 h. Insoluble material is collected by centrifugation (12,000 x g for 10 min), and the supernatant is discarded. The insoluble residue is reextracted with 2 volumes (original tumor weight) of Buffer A for 30 min with stirring at 4°C. Insoluble material is again collected by centrifugation, and the supernatant fraction is discarded. The insoluble material is then suspended in 6 volumes of Buffer B (6 M urea, 0.1 M 6-aminohexanoic acid, 0.04 M ethylenediaminetetraacetic acid (EDTA), 0.002 M PMSF, and 0.05 M Tris-HCl, pH 6.8), homogenized with an electric homogenizer (Polytron) for 30 s, and stirred for 2 h at 4°C. The mixture is centrifuged to remove insoluble material, and the supernatant is retained. The insoluble material is reextracted with 2 volumes of Buffer B. The mixture is centrifuged, and the supernatant is combined with the previous supernatant. 35 S-HSPG is isolated from the Buffer B supernatant by sequential chromatography on anion exchange and gel filtration columns. The Buffer B supernatant is dialyzed overnight against 10 volumes of 6 M urea, 0.15 M ΝaCl, 0.05 M Tris-HCl, pH 6.8, and is adjusted to contain 0.5% non-ionic detergent (Triton X-100). This supernatant (from 11 g tumor) is chromatographed on a 30 ml column of anion exchange resin (DEAE-Sephacel) equilibrated with 6 M urea, 0.15 M ΝaCl, 0.05% Triton X-100, 0.05 M Tris-HCl, pH 6.8. After loading the supernatant and washing with the equilibration buffer, the column is developed with a 250 ml linear gradient between 0.15 M ΝaCl and 1.15 M ΝaCl (How = 2.0 ml/min). Fractions are sampled for radioactivity, and those containing the 35 SO 4 label that elutes from the DEAE- Sephacel between 0.4 M and 0.8 M ΝaCl are pooled. The proteoglycan is precipitated by the addition of 4 volumes of 100% EtOH at -20°C overnight. The precipitate is collected by centrifugation and is solubilized in 1 ml of Buffer C (4 M Gu-HCl, 20 mM Tris-HCl, pH 7.2). This solubilized peUet is used for chromatography on a calibrated gel filtration column (1.0 x 50 cm column of Superose 6; Pharmacia) equilibrated in Buffer C (Flow = 0.5 ml/min). Fractions are sampled for radioactivity, and those containing the 35 SO 4 label that elutes with a molecular weight > 70 kD were pooled. The proteoglycan is precipitated with 100% EtOH as described above. The pellet is dissolved in 3 ml PBS, and dialyzed against 3 x 100 volumes of PBS. Each preparation of 35 S-HSPG is confirmed to be > 98% heparan sulfate by susceptibility to low pH nitrous acid degradation (Shiveley and Conrad, Biochemistry 15: 3932-3942, 1976). Example 3: Preparation of cDΝA encoding Heparanase. Media is removed from cultured HEL (HEL 92.1.7; Human erythroleukemia; ATCC No. TIB 180) cells stimulated with lOnM phorbol 12-myristate 13-acetate (Sigma Chemical Co., St. Louis, MO) and the cells scraped from the dish and pelleted by centrifugation. The pellet is extracted with 200wl of TRI reagent (Molecular Research Center Inc. Cincinnati, OH) and the total cellular RNA is prepared according to the manufacturer's instructions. To prepare first strand synthesis the reverse transcriptase reaction was performed with lOwl of total cellular RNA in the presence of 4«1 of 5x transcripiase buffer (Bethesda Research Laboratories, Gaithersburg, MD), lκl 0.2mM DTT, 4κl random hexanucleotides (Amersham Corp. Arlington Heights, ILL), and lκl lOmM dNTP (BRL). This solution is heated to 95 degrees C for 5 minutes and then placed on ice. To this is added lκl RNAsin and lwl reverse transcriptase (M-MLV), (Promega, Madison WI). This is incubated at 37 degrees for 60 minutes and then placed on ice. The polymerase chain reaction is carried out as follows. To 3 l of the first strand (above) is added lwl of each Primer (see below), 77 wl of water lOwl lOx PCR buffer (Perkin Elmer Cetus, Norwalk CT) and 2«1 each dNTP. This solution is heat denatured at 95 degrees C and 1«1 Amplitaq DNA polymerase (Perkin Elmer Cetus) is added. Hybridization temperature begins at 72 degrees and is lowered by one degree per cycle until reaching 55 degrees. Each hybridization step is followed with a constant elongation temperature of 72 degrees. Upon completion the solution is left at 0 degrees until storage at -20 degrees. The products of the PCR reaction are electrophoresed on 3% NuSieve, 1% agarose gels and bands of expected size are excised and purified by standard procedures. Primers: Platelet Basic Protein: TGG ACT AGT ATG TCC TCC ACC AAA GGA CAA ACT AA CTAP IH: TGG ACT AGT ATG AAC TTG GCG AAA GAG GA B-thrombglobulin: TGG ACT AGT ATG GGC AAA GAG GAA AGT CTA GAC AG NAP-2: TGG ACT AGT ATG GAA CTC CGC TGC ATG TGT ATA AA Example 4: Preparation of cDNA encoding Heparanase. Media is removed from cultured leukocyte-derived cells [e.g., lymphocytes, neutrophils, platelets, Jurkatt lymphoma cells, Dami ceUs (Greenberg et al., Blood 72:1968-1977, (1988)], stimulated 7'ith Concanavalin A or phorbol 12-myristate 13 acetate (Sigma Chemical Co., St. Louis, MO) and the cells scraped from the dish and pelleted by centrifugation. The pellet is extracted with 200«1 of TRI reagent (Molecular Research Center Inc. Cincinnati, OH) and the total cellular RNA is prepared according to the manufacturer's instructions. To prepare first strand synthesis the reverse transcriptase reaction was performed with 10κl of total cellular RNA in the presence of 4κl of 5x transcriptase buffer (Bethesda Research Laboratories, Gaithersburg, MD), lwl 0.2mM DTT, 4wl random hexanucleotides (Amersham Corp. Arlington Heights, ELL), and lwl lOmM dNTP (BRL). This solution is heated to 95 degrees C for 5 minutes and then placed on ice. To this is added 1«1 RNAsin and lwl reverse transcriptase (M-MLV), (Promega, Madison Wl). This is incubated at 37 degrees for 60 minutes and then placed on ice. The polymerase chain reaction is carried out as follows. To 3wl of the first strand (above) is added lwl of each Primer (see below), 77wl of water lOwl lOx PCR buffer (Perkin Elmer Cetus, Norwalk CT) and 2wl each dNTP. This solution is heat denatured at 95 degrees C and lwl Amplitaq DNA polymerase (Perkin Elmer Cetus) is added. Hybridization temperature begins at 72 degrees and is lowered by one degree per cycle until reaching 55 degrees. Each hybridization step is followed with a constant elongation temperature of 72 degrees. Upon completion the solution is left at 0 degrees until storage at -20 degrees. The products of the PCR reaction are electrophoresed on 3% NuSieve, 1% agarose gels and bands of expected size are excised and purified by standard procedures. Primers: Platelet Basic Protein: TGG ACT AGT ATG TCC TCC ACC AAA GGA CAA ACT AA CTAP IH: TGG ACT AGT ATG AAC TTG GCG AAA GAG GA B-thrombglobulin: TGG ACT AGT ATG GGC AAA GAG GAA AGT CTA GAC AG NAP-2: TGG ACT AGT ATG GAA CTC CGC TGC ATG TGT ATA AA All temperatures expressed throughout the subject specification are in degrees Centigrade. The cDNA encoding heparanase is preferably cloned into a vector designed for expression in eukaryotic cells, rather than into a vector designed for expression in prokaryotic cells (e.g. E. coli). Eukaryotic cells are preferred for expression of genes obtained from higher eukaryotes because the signals for synthesis, processing, and secretion of these proteins are usually recognized, whereas this is often not true for prokaryotic hosts (Ausubel, et al, ed., in Short Protocols in Molecular Biology, 2nd edition, John Wiley & Sons, publishers, pg.16-49, 1992.). Eukaryotic hosts may include, but are not limited to, the foUowing: insect cells, African green monkey kidney cells (COS cells), Chinese hamster ovary cells (CHO cells), and Murine 3T3 fibroblasts. Experiments demonstrating that a synthetic peptide of CTAP-HI/NAP-2 or antisera raised against a synthetic peptide of CTAP-IH/NAP-2 inhibit the heparanase activity of CTAP- πi/NAP-2 suggest that the amino acids participating in enzymatic catalysis are contained in a C- terminal region of the enzyme. Peptide Synthesis: A C-terminal peptide contained within the sequences known for CTAP-IH (SEQ ID NO: 1), Platelet Basic Protein (SEQ ID NO: 3), β-thromboglobulin (SEQ ID NO: 5), and NAP-2 (SEQ ID NO: 7), and an N-terminal peptide contained within the sequences known for CTAP-iπ (SEQ ID NO: 1) and Platelet Basic Protein (SEQ ID NO: 3) were synthesized according to standard procedures. The N-terminal peptide has the following sequence (SEQ ID NO: 41: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Cys, in which the final Cys residue was added to regions of known sequence (SEQ ID NOS: 1,3) for the purpose of conjugation to a carrier protein. The C-terminal peptide has the following sequence (SEQ ID NO: 42): Cys Asn Gin Val Glu Val He Ala Thr Leu Lys Asp Gly Arg Lys He Cys Leu Asp Pro Asp Ala Pro Arg He Lys Lys He Val Gin Lys Lys encoded by the cDNA sequence (SEQ ID NO: 43) of TGCAACCAAG TCGA GTGAT AGCCACACTG AAGGATGGGA GGAAAATCTG CCTGGACCCA GAT TCCCA GAATCAAGAA AATTGTACAG AAAAAA. These peptides (SEQ ID NOS: 41 and 42) were produced by stepwise solid phase peptide synthesis on an Applied Biosystems 430A Peptide Synthesizer. The 9- fluoroenylmethyloxycarbonyl (Fmoc) group was used as the N α amino protecting group, and temporary side-chain protectin groups were as follows: Arg (Pmc), Asn (Trt), Asp (OtBu), Gin (Trt), Glu (OtBu), His (Trt), Lys (Boc), Ser (tBu), Thr (tBu). Each residue was single coupled using a HBTU/NMP protocol and capped with acetic anhydride before the next synthesis cycle. After removal of the N-terminal Fmoc group, temporary side-chain protecting groups were removed and the peptide cleaved from the resin by treatment with 95% TFA/5% scavengers (ethyl methyl sulfide/ani&- -,2-ethanedithiol, 1:3:1) for two hours at room temperature. The crude peptides were precipitated from the cleavage solution with cold diethyl ether. The precipitated peptide was collected on a sintered glass funnel, washed with diethyl ether, dissolved in dilute acetic acid, evaporated to dryness under reduced pressure, and the residue was redissolved and lyophillized from glacial acetic acid. The crude peptides were purified by preparative reverse phase chromatography on a Phenomenex C-18 column (22.5 x 250 mm) using a water/acetonitrile gradient, each phase containing 0.1% trifluoracetic acid (TFA). Clean fractions, as determined by analytical HPLC, were pooled, the acetonitrile was evaporated under reduced pressure, and the aqueous solution was lyophillized. The purified peptides were characterized by time of flight or FAB mass spectroscopy. Further, SEQ ID NO: 42 can be produced by recombinant DNA methodology as stated in Procedure A (page 21). Antisera Production: The synthetic peptides of CTAP-HI/NAP-2 were conjugated to keyhole limpet hemocyanin utilizing a maleimide-activated carrier protein (Pierce Chemical Co. #77107). 300 μg of conjugated peptides were injected into chickens using Freunds complete adjuvant. The antisera were collected 5 weeks after initial immunization. Specific recognition by the antisera of commercial CTAP-IH (2.5 μg, (Celsus Laboratories Inc., Cincinnati, Ohio; Cat #. 41705), isolated heparanase (1.5 μg), and 10 μl of the platelet supernatant used for purification was achieved by separating the proteins on a reducing 18% polyacrylamide gel (Novex), transferring to nitrocellulose, and incubating with the pre-immune or antisera (1:1500), followed by incubation with a peroxidase labeled goat anti-chicken IgG (1:500; Kierkegaard and Perry) in the presence of PBS containing 5% dry milk and 0.05% Tween-20. The pre-immune sera did not recognize 7 - 10 kD proteins in the commercial CTAP-HI, isolated heparanase, or platelet supernatants. Inhibition of heparanase activity by the C-terminal synthetic peptide (SEO ID NO: 42) or antisera: For experiments designed to determine whether the peptide antisera was able to inhibit heparanase activity, the pre-immune and antisera were exchanged into 0.15M NaCl, 0.01M sodium phoshate buffer, pH 7.4 (PBS) using a 100 kD cut-off membrane in order to remove low molecular weight chicken heparanase normally present in the serum. Aliquots of isolated heparanase (15 ng) were pre-incubated for 30 min with 2 μl of either pre-immune or anti-CTAP-HI antisera before adding the 35 S-HSPG to determine heparanase activity. In the presence of the pre-immune sera, the isolated protein had 14.3 ± 0.1 units of heparanase activity, while in the presence of the C-terminal peptide antisera, only 0.8 ± 0.2 units of heparanase were detected (p < 0.001; results confirmed in a second experiment). The N-terminal peptide antiserum was not able to neutralize the heparanase activity. Similar results were obtained when the ability of the synthetic peptides to neutralize heparanase activity was examined. Heparanase assays conducted with 3 nM enzyme, 47 nM 35 S-HSPG substrate, and varying concentrations of peptides showed that heparanase activity was only 5% of control values in the presence of 250 μM C-terminal peptide. By contrast, heparanase activity in the presence of 250 μM of either the N-terminal peptide or an unrelated peptide (PLALWAR) was 67% of control values. The ability of both the C-terminal peptide (SEQ ID NO: 42) or antisera from a chicken immunized with the C-terminal synthetic peptide to neutralize heparanase activity demonstrates conclusively that CTAP-πi and NAP-2 possess heparanase activity, and suggests that the C-terminal region is essential for catalysis. Modeling of this domain (SEQ ID NO: 42) can be used in the identification of potent peptide-mimetic compounds capable of inhibiting this enzyme activity. Computer assisted modeling can be accomplished using programs for automated docking of molecules within 3D databases, as described in DesJarlais, R.L., Sheridan, R.P., Seibel, G.L., Dixon, J.S., Kuntz, I.D., Venkataraghavan, R., "Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure"; J. Med. Chem. 31:722-729, 1988. Also, automated de novo construction of ligands that can bind the catalytic site as described in Moon, J.B., Howe, W.J., "Computer design of bioactive molecules: a method for receptor-based de novo ligand design"; Proteins: Struct., Funct., and Genetics, 11:314-328, 1981. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: Hooge erf, Arlene J. Ledbetter, Steven R. (ii) TITLE OF INVENTION: USE OF HEPARANASE TO IDENTIFY AND ISOLATE ANTI-HEPARANASE COMPOUNDS (iii) NUMBER OF SEQUENCES: 43 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: The Upjohn Company, Intellectual Property Law (B) STREET: 301 Henrietta (C) CITY: Kalamazoo (D) STATE: MI (E) COUNTRY: USA (F) ZIP: 49001 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.25 (Vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Jameson, William G. (B) REGISTRATION NUMBER: 27,199 (C) REFERENCE/DOCKET NUMBER: 4731.1 CP (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 616/385-7561 (B) TELEFAX: 616/385-6897 (C) TELEX: 224401 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 85 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:1: Asn Leu Ala Lys Gly s Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala 1 5 10 15 Glu Leu Arg Cys Met Cys lie Lys Thr Thr Ser Gly lie His Pro Lys 20 25 30 Asn lie Gin Ser Leu Glu Val lie Gly Lys Gly Thr His Cys Asn Gin 35 40 45 Val Glu Val lie Ala Thr Leu Lys Asp Gly Arg Lys lie Cys Leu Asp 50 55 60 Pro Asp Ala Pro Arg lie Lys Lys lie Val Gin Lys Lys Leu Ala Gly 65 70 75 80 Asp Glu Ser Ala Asp 85 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 255 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: AACTTGGCGA AAGGCAAAGA GGAAAGTCTA GACAGTGACT TGTATGCTGA ACTCCGCTGC 60 ATGTGTATAA AGACAACCTC TGGAATTCAT CCCAAAAACA TCCAAAGTTT GGAAGTGATC 120 GGGAAAGGAA CCCATTGCAA CCAAGTCGAA GTGATAGCCA CACTGAAGGA TGGGAGGAAA 180 ATCTGCCTGG ACCCAGATGC TCCCAGAATC AAGAAAATTG TACAGAAAAA ATTGGCAGGT 240 GATGAATCTG CTGAT 255 (2) INFORMATION FOR SEQ ID NO:3 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 94 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: Ser Ser Thr Lys Gly Gin Thr Lys Arg Asn Leu Ala Lys Gly Lys Glu 1 5 10 15 Glu Ser Leu Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys lie 20 25 30 Lys Thr Thr Ser Gly lie His Pro Lys Asn lie Gin Ser Leu Glu Val 35 40 45 lie Gly Lys Gly Thr His Cys Asn Gin Val Glu Val lie Ala Thr Leu 50 55 60 Lys Asp Gly Arg Lys lie Cys Leu Asp Pro Asp Ala Pro Arg lie Lys 65 70 75 80 Lys lie Val Gin Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp 85 90 (2) INFORMATION FOR SEQ ID NO:4 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 282 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:4 : TCCTCCACCA AAGGACAAAC TAAGAGAAAC TTGGCGAAAG GCAAAGAGGA AAGTCTAGAC 60 AGTGACTTGT ATGCTGAACT CCGCTGCATG TGTATAAAGA CAACCTCTGG AATTCATCCC 120 AAAAACATCC AAAGTTTGGA AGTGATCGGG AAAGGAACCC ATTGCAACCA AGTCGAAGTG 180 ATAGCCACAC TGAAGGATGG GAGGAAAATC TGCCTGGACC CAGATGCTCC CAGAATCAAG 240 AAAATTGTAC AGAAAAAATT GGCAGGTGAT GAATCTGCTG AT 282 (2) INFORMATION FOR SEQ ID NO:5 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 81 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys 1 5 10 15 Met Cys lie Lys Thr Thr Ser Gly lie His Pro Lys Asn lie Gin Ser 20 25 30 Leu Glu Val lie Gly Lys Glv Thr His Cys Asn Gin Val Glu Val lie 35 40 45 Ala Thr Leu Lys Asp Gly Arg Lys lie Cys Leu Asp Pro Asp Ala Pro 50 55 60 Arg lie Lys Lys lie Val Gin Lys Lys Leu Ala Gly Asp Glu Ser Ala 65 70 75 80 Asp (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 24T base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: GGCAAAGAGG AAAGTCTAGA CAGTGACTTG TATGCTGAAC TCCGCTGCAT GTGTATAAAG 60 ACAACCTCTG GAATTCATCC CAAAAACATC CAAAGTTTGG AAGTGATCGG GAAAGGAACC 120 CATTGCAACC AAGTCGAAGT GATAGCCACA CTGAAGGATG GGAGGA- T CTGCCTGGAC 180 CCAGATGCTC CCAGAATCAA GAAAATTGTA CAGAAAAAAT TGGCAGGTGA TGAATCTGCT 240 GAT 243 (2) INFORMATION FOR SEQ ID NO: : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 69 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: Glu Leu Arg Cys Met Cys lie Lys Thr Thr Ser Gly lie His Pro Lys 1 5 10 15 Asn lie Gin Ser Leu Glu Val lie Gly Lys Gly Thr His Cys Asn Gin 20 25 30 Val Glu Val lie Ala Thr Leu Lys Asp Gly Arg Lys lie Cys Leu Asp 35 40 45 Pro Asp Ala Pro Arg lie Lys Lys lie Val Gin Lys Lys Leu Ala Gly 50 55 60 Asp Glu Ser Ala Asp 65 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 207 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: GAACTCCGCT GCATGTGTAT AAAGACAACC TCTGGAATTC ATCCCAAAAA CATCCAAAGT 60 TTGGAAGTGA TCGGGAAAGG AACCCATTGC AACCAAGTCG AAGTGATAGC CACACTGAAG 120 GATGGGAGGA AAATCTGCCT GGACCCAGAT GCTCCCAGAA TCAAGAAAAT TGTACAGAAA 180 AAATTGGCAG GTGATGAATC TGCTGAT 207 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala 1 5 10 15 Glu Leu Arg (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: Ser Ser Thr Lys Gly Gin Thr Lys Arg Asn Leu Ala Lys Gly Lys Glu 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear ( i) SEQUENCE DESCRIPTION: SEQ ID NO:11: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Tyr Ala 1 5 10 15 Glu (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 101 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: singxe (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: Met Ser Ser Ala Ala Gly Phe Cys Ala Ser Arg Pro Gly Leu Leu Phe 1 5 10 15 Leu Gly Leu Leu Leu Leu Pro Leu Val Val Ala Phe Ala Ser Ala Glu 20 25 30 Ala Glu Glu Asp Gly Asp Leu Gin Cys Leu Cys Val Lys Thr Thr Ser 35 40 45 Gin Val Arg Pro Arg His lie Thr Ser Leu Glu Val lie Lys Ala Gly 50 55 60 Pro His Cys Pro Thr Ala Gin Leu lie Ala Thr Leu Lys Asn Gly Arg 65 70 75 80 Lys lie Cys Leu Asp Leu Gin Ala Pro Leu Tyr Lys Lys lie lie Lys 85 90 95 Lys Leu Leu Glu Ser 100 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 439 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: CCGCAGCATG AGCTCCGCAG CCGGGTTCTG CGCCTCACGC CCCGGGCTGC TGTTCCTGGG 60 GTTGCTGCTC CTGCCACTTG TGGTCGCCTT CGCCAGCGCT GAAGCTGAAG AAGATGGGGA 120 CCTGCAGTGC CTGTGTGTGA AGACCACCTC CCAGGTCCGT CCCAGGCACA TCACCAGCCT 180 GGAGGTGATC AAGGCCGGAC CCCACTGCCC CACTGCCCAA CTGATAGCCA CGCTGAAGAA 240 TGGAAGGAAA ATTTGCTTGG ACCTGCAAGC CCCGCTGTAC AAGAAAATAA TTAAGAAACT 300 TTTGGAGAGT TAGCTACTAG CTGCCTACGT GTGTGCATTT GCTATATAGC ATACTTCTTT 360 TTTCCAGTTT CAATCTAACT GTGAAAGAAA CTTCTGATAT TTGTGTTATC CTTATGATTT 420 TAAATAAACA AAATAAATC 439 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 101 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: Met Asn Gin Thr Ala lie Leu lie Cys Cys Leu lie Phe Leu Thr Leu 1 5 10 15 Ser Gly lie Gin Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys 20 25 30 lie Ser lie Ser Asn Gin Pro Val Asn Pro Val Asn Pro Arg Ser Leu 35 40 45 Glu Lys Leu Glu lie lie Pro Ala Ser Gin Phe Cys Pro Arg Val Glu 50 55 60 lie lie Ala Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro 65 70 75 80 Glu Ser Lys Ala lie Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met 85 90 95 Ser Lys Arg Ser Pro 100 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 650 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: GAGACATTCC TCAATTGCTT AGACATATTC TGAGCCTACA GCAGAGGAAC CTCCAGTCTC 60 AGCACCATGA ATCAAACTGC GATTCTGATT TGCTGCCTTA TCTTTCTGAC TCTAAGTGGC 120 ATTCAAGGAG TACCTCTCTC TAGAACCGTA CGCTGTACCT GCATCAGCAT TAGTAATCAA 180 CCTGTTAATC CAAGGTCTTT AGAAAAACTT GAAATTATTC CTGCAAGCCA ATTTTGTCCA 240 CGTGTTGAGA TCATTGCTAC AATGAAAAAG AAGGGTGAGA AGAGATGTCT GAATCCAGAA 300 TCGAAGGCCA TCAAGAATTT ACTGAAAGCA GTTAGCAAGG AAATGTCTAA AAGATCTCCT 360 TAAAACCAGA GGGGAGCAAA ATCGATGCAG TGCTTCCAAG GATGGACCAC ACAGAGGCTG 420 CCTCTCCCAT CACTTCCCTA CATGGAGTAT ATGTCAAGCC ATAATTGTTC TTAGTTTGCA 480 GTTACACTAA AAGGTGACCA ATGATGGTCA CCAAATCAGC TGCTACTACT CCTGTAGGAA 540 GGTTAATGTT CATCATCCTA AGCTATTCAG TAATAACTCT ACCCTGGCAC TATAATGTAA 600 GCTCTACTGA GGTGCTATGT TCTTAGTGGA TGTTCTGACC CTGCTTCAAA 650 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 107 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: f ~]Q ID NO:16: Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala 20 25 30 Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr 35 40 45 Leu Gin Gly lie His Pro Lys Asn lie Gin Ser Val Asn Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gin Thr Glu Val lie Ala Thr Leu Lys Asn 65 70 75 80 Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro lie Val Lys Lys lie 85 90 95 lie Glu Lys Met Leu Asn Ser Asp Lys Ser Asn 100 105 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1050 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: CTCGCCAGCT CTTCCGCTCC TCTCACAGCC GCCAGACCCG CCTGCTGAGC CCCATGGCCC 60 GCGCTGCTCT CTCCGCCGCC CCCAGCAATC CCCGGCTCCT GCGAGTGGCA CTGCTGCTCC 120 TGCTCCTGGT AGCCGCTGGC CGGCGCGCAG CAGGAGCGTC CGTGGCCACT GAACTGCGCT 180 GCCAGTGCTT GCAGACCCTG CAGGGAATTC ACCCCAAGAA CATCCAAAGT GTGAACGTGA 240 AGTCCCCCGG ACCCCACTGC GCCCAAACCG AAGTCATAGC CACACTCAAG AATGGGCGGA 300 AAGCTTGCCT CAATCCTGCA TCCCCCATAG TTAAGAAAAT CATCGAAAAG ATGCTGAACA 360 GTGACAAATC CAACTGACCA GAAGGGAGGA GGAAGCTCAC TGGTGGCTGT TCCTGAAGGA 420 GGCCCTGCCC TTATAGGAAC AGAAGAGGAA AGAGAGACAC AGCTGCAGAG GCCACCTGGA 480 TTGTGCCTAA TGTGTTTGAG CATCGCTTAG GAGAAGTCTT CTATTTATTT ATTTATTCAT 540 TAGTTTTGAA GATTCTATGT TAATATTTTA GGTGTAAAAT AATTAAGGGT ATGATTAACT 600 CTACCTGCAC ACTGTCCTAT TATATTCATT CTTTTTGAAA TGTCAACCCC AAGTTAGTTC 660 AATCTGGATT CATATTTAAT TTGAAGGTAG AATGTTTTCA AATGTTCTCC AGTCATTATG 720 TTAATATTTC TGAGGAGCCT GCAACATGCC AGCCACTGTG ATAGAGGCTG GCGGATCCAA 780 GCAAATGGCC AATGAGATCA TTGTGAAGGC AGGGGAATGT ATGTGCACAT CTGTTTTGTA 840 ACTGTTTAGA TGAATGTCAG TTGTTATTTA TTGAAATGAT TTCACAGTGT GTGGTCAACA 900 TTTCTCATGT TGAAACTTTA AGAACTAAAA TGTTCTAAAT ATCCCTTGGA CATTTTATGT 960 CTTTCTTGTA AGGCATACTG CCTTGTTTAA TGGTAGTTTT ACAGTGTTTC TGGCTTAGAA 1020 CAAAGGGGCT TAATTATTGA TGTTTTCGGA 1050 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 102 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:18 Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala 20 25 30 Ala Gly Ala Pro Lys Ala Thr Glu Lys Arg Cys Gin Cys Lys Gin Thr 35 40 45 Leu Gin Gly lie His Leu Lys Asn lie Gin Ser Val Lys Val Lys Ser 50 55 60 Pro Gly Pro His Cys Ala Gin Thr Glu Val lie Ala Thr Leu Lys Asn 65 70 75 80 Gly Gin Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys lie 85 90 95 lie Glu Lys Met Leu Lys 100 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1081 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: CTCTCCTCCT CGCACAGCCG CTCGAACCGC CTGCTGAGCC CCATGGCCCG CGCCACGCTC 60 TCCGCCGCCC CCAGCAATCC CCGGCTCCTG CGGGTGGCGC TGCTGCTCCT GCTCCTGGTG 120 GCCGCCAGCC GGCGCGCAGC AGGAGCGCCC CTGGCCACTG AACTGCGCTG CCAGTGCTTG 180 CAGACCCTGC AGGGAATTCA CCTCAAGAAC ATCCAAAGTG TGAAGGTGAA GTCCCCCGGA 240 CCCCACTGCG CCCAAACCGA AGTCATAGCC ACACTCAAGA ATGGGCAGAA AGCTTGTCTC 300 AACCCCGCAT CGCCCATGGT TAAGAAAATC ATCGAAAAGA TGCTGAAAAA TGGCAAATCC 360 AACTGACCAG AAGGAAGGAG GAAGCTTATT GGTGGCTGTT CCTGAAGGAG GCCCTGCCCT 420 TACAGGAACA GAAGAGGAAA GAGAGACACA GCTGCAGAGG CCACCTGGAT TGCGCCTAAT 480 GTGTTTGAGC ATCACTTAGG AGAAGTCTTC TATTTATTTA TTTATTTATT TATTTGTTTG 540 TTTTAGAAGA TTCTATGTTA ATATTTTATG TGTAAAATAA GGTTATGATT GAATCTACTT 600 GCACACTCTC CCATTATATT TATTGTTTAT TTTAGGTCAA ACCCAAGTTA GTTCAATCCT 660 GATTCATATT TAATTTGAAG ATAGAAGGTT TGCAGATATT CTCTAGTCAT TTGTTAATAT 720 TTCTTCGTGA TGACATATCA CATGTCAGCC ACTGTGATAG AGGCTGAGGA ATCCAAGAAA 780 ATGGCCAGTG AGATCAATGT GACGGCAGGG AAATGTATGT GTGTCTATTT TGTAACTGTA 840 AAGATGAATG TCAGTTGTTA TTTATTGAAA TGATTTCACA GTGTGTGGTC AACATTTCTC 900 ATGTTGAAGC TTTAAGAACT AAAATGTTCT AAATATCCCT TGGACATTTT ATGTCTTTCT 960 TGTAAGGCAT ACTGCCTTGT TTAATGTTAA TTATGCAGTG TTTCCCTCTG TGTTAGAGCA 1020 GAGAGGTTTC GATATTTATT GATGTTTTCA CAAAGAACAG GAAAATAAAA TATTTAAAAA 1080 T 1081 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 107 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: Met Ala His Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu 1 5 10 15 Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala 20 25 30 Ala Gly Ala Ser Val Val Thr Glu Leu Arg Cys Gin Cys Leu Gin Thr 35 40 45 Leu Gin Gly lie His Leu Lys Asn lie Gin Ser Val Asn Val Arg Ser 50 55 60 Pro Gly Pro His Cys Ala Gin Thr Glu Val lie Ala Thr Leu Lys Asn 65 70 75 80 Gly Lys Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Gin Lys lie 85 90 95 lie Glu Lys lie Leu Asn Lys Gly Ser Thr Asn 100 105 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 988 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: CTCGCACAGC TTCCCGACGC GTCTGCTGAG CCCCATGGCC CACGCCACGC TCTCCGCCGC 60 CCCCAGCAAT CCCCGGCTCC TGCGGGTGGC GCTGCTGCTC CTGCTCCTGG TGGCCGCCAG 120 CCGGCGCGCA GCAGGAGCGT CCGTGGTCAC TGAACTGCGC TGCCAGTGCT TGCAGACACT 180 GCAGGGAATT CACCTCAAGA ACATCCAAAG TGTGAATGTA AGGTCCCCCG GACCCCACTG 240 CGCCCAAACC GAAGTCATAG CCACACTCAA GAATGGGAAG AAAGCTTGTC TCAACCCCGC 300 ATCCCCCATG GTTCAGAAAA TCATCGAAAA GATACTGAAC AAGGGGAGCA CCAACTGACA 360 GGAGAGAAGT AAGAAGCTTA TCAGCGTATC ATTGACACTT CCTGCAGGGT GGTCCCTGCC 420 CTTACCAGAG CTGAAAATGA AAAAGAGAAC AGCAGCTTTC TAGGGACAGC TGGAAAGGAC 480 TTAATGTGTT TGACTATTTC TTACGAGGGT TCTACTTATT TATGTATTTA TTTTTGAAAG 540 CTTGTATTTT AATATTTTAC ATGCTGTTAT TTAAAGATGT GAGTGTGTTT CATCAAACAT 600 AGCTCAGTCC TGATTATTTA ATTGGAATAT GATGGGTTTT AAATGTGTCA TTAAACTAAT 660 ATTTAGTGGG AGACCATAAT GTGTCAGCCA CCTTGATAAA TGACAGGGTG GGGAACTGGA 720 GGGTGGGGGG ATTGAAATGC AAGCAATTAG TGGATCACTG TTAGGGTAAG GGAATGTATG 780 TACACATCTA TTTTTTATAC TTTTTTTTTA AAAAAAGAAT GTCAGTTGTT ATTTATTCAA 840 ATTATCTCAC ATTATGTGTT CAACATTTTT ATGCTGAAGT TTCCCTTAGA CATTTTATGT 900 CTTGCTTGTA GGGCATAATG CCTTGTTTAA TGTCCATTCT GCAGCGTTTC TCTTTCCCTT 960 GGAAAAGAGA ATTTATCATT ACTGTTAC 988 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 97 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu lie Ser 1 5 10 15 Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu 20 25 30 Arg Cys Gin Cys lie Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe 35 40 45 lie Lys Glu Leu Arg Val lie Glu Ser Gly Pro His Cys Ala Asn Thr 50 55 60 Glu lie lie Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro 65 70 75 80 Lys Glu Asn Trp Val Gin Arg Val Val Glu Lys Phe Leu Lys Arg Ala 85 90 95 Glu (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 291 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: ATGACTTCCA AGCTGGCCGT GGCTCTCTTG GCAGCCTTCC TGATTTCTGC AGCTCTGTGT 60 GAAGGTGCAG TTTTGCCAAG GAGTGCTAAA GAACTTAGAT GTCAGTGCAT AAAGACATAC 120 TCCAAACCTT TCCACCCCAA ATTTATCAAA GAACTGAGAG TGATTGAGAG TGGACCACAC 180 TGCGCCAACA CAGAAATTAT TGTAAAGCTT TCTGATGGAA GAGAGCTCTG TCTGGACCCC 240 AAGGAAAACT GGGTGCAGAG GGTTGTGGAG AAGTTTTTGA AGAGGGCTGA G 291 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 78 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Ala Gly Pro Ala Ala Ala Val Leu Arg Glu Lys Arg Cys Val Cys Leu 1 5 10 15 Gin Thr Thr Gin Gly Val His Pro Lys Met lie Ser Asn Leu Gin Val 20 25 30 Phe Ala lie Gly Pro Gin Cys Ser Lys Val Glu Val Val Ala Ser Leu 35 40 45 Lys Asn Gly Lys Glu lie Cys Leu Asp Pro Glu Ala Pro Phe Leu Lys 50 55 60 Lys Val lie Gin Lys lie Leu Asp Gly Gly Asn Lys Glu Asn 65 70 75 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 216 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: GTGTTGCGGG AACTGCGGTG CGTGTGTTTA CAGACCACGC AGGGAGTTCA TCCCAAAATG 60 ATCAGTAATC TGCAAGTGTT CGCCATAGGC CCACAGTGCT CCAAGGTGGA AGTGGTAGCC 120 TCCCTGAAGA ACGGGAAGGA AATTTGTCTT GATCCAGAAG CCCCTTTTCT AAAGAAAGTC 180 ATCCAGAAAA TCCTCGACGG CGGCAACAAA GAAAAC 216 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 93 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: Met Gin Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala 1 5 10 15 Leu Cys Asn Gin Val Leu Ser Ala Pro Leu Ala Ala Asp Thr Pro Thr 20 25 30 Ala Cys Cys Phe Ser Tyr Thr Ser Arg Gin lie Pro Gin Asn Phe lie 35 40 45 Ala Asp Tyr Phe Glu Thr Ser Ser Gin Cys Ser Lys Pro Ser Val lie 50 55 60 Phe Leu Thr Lys Arg Gly Arg Gin Val Cys Ala Asp Pro Ser Glu Glu 65 70 75 80 Trp Val Gin Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala 85 90 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4788 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: GAATTCAAGG CCTGTCCTGG TTTGGTCCCA ATTTACCTTT ATCATCCATA TTCACCCCCA 60 CTGCTCTGCA GCTCCACTGA AGCACCCCCT CTTTCCTCTG AGCCACAATG TCACACCCAG 120 GACTCTGCCT CAGCTGGGCC TCCACTGCCC ACCCATCTAT AGATGCCTAA ATCCCGGGCA 180 GTTATCCAGA CACAACTAAA GTTCCATCCC TTCCATGAAG CCTTCCCCAA CCCTCTGGTG 240 GAAGGTCACT TCTTCCTCAT GGGGTTCTGA GCTTTCATTT CTTTTTCTAC TAAGAGTTTT 300 ACAATTACCT GTTCATACAC TCTACCTGCC CCCATGAGAC CAGGGGCATC TCAGAAACAA 360 AGATCATTAA AACCAACTAA ATCTATTTCT CATTATAAAA TGAGATATGC TGATTGATTG 420 CAAAATAATA AAATAACAAA GTATGGAAAA GAAAAAAAAA AGCATATAAT C73GCTGAGA 480 AGGTAGAGAC CCTTCCACAC CACTGAAATT ATGTGTTGAA AAGAATAAGG AAAAAACTGC 540 TTCAGTTTGG CATTATTTAT GTAAGTATAG TATAGGATCC TTAAAATGGT TCAAAGAAAT 600 GGGAAATCAA GACTTCATTT TGGCAAAGCC ATTGAACAGA AACTGTAGCA TATTTATCAG 660 TAATTTCTTT CAGATTAAAC AACTGACAAC AACCCACTTT TCAACCAGTG ATGTTGGAAA 720 TGTTTTAAAA CAAAATTAGT TCATAAATTT GTGGGTTGAC CAAGAAGGTA ATAAAGTCTC 780 ACTAAATAAA ATGAGGAAAA TTCAGAAAAA GAAAAAAATA AGAAAATAAA TCACCCATGG 840 ATCTAAGCAC TATTCATTCT TTAAGGCATG TATTTCCAAG CCTTTTAATT TTTTCATGCC 900 TAGAGTTGGC ATGGCATATA TATATCTTTA TACAATTCTT CAAATTTTAT AGAATTTGTA 960 TAATGTTTTA TCTTGCTTTT TTTTTAACCA CTGATGTTAT AAGCATATTT ATGCCACTTC 1020 ATTCACGTTA GAGACTTAAT AATAAAGGAT CTTGTGGATA ATTTATCATT CCCTGATAGA 1080 GAAAAATTTA GCTTTGCTTA TTTTAGAGTT ATAAATGATG CTGGGTCAGG TATCTTTATG 1140 TTTGAAGATG GCTCCATATT TGGGTTGTTT CCACAGAACT CTTTCCAGAA ATGCTTTTTC 1200 TAGGTTAATG GCTACACATA TTTCTAGGCA CCTGACATAC TGACACCCAC CTCTAAAGTA 1260 TTTTTATGAT CCACAACTAG CGTTTAACAC AGCGCCCC "! TCACTCCGAG ACTAATAAAT 1320 AGACAAATGA CTGAAACGTG ACCTCATGCT TTCTATTCC-.' CCAGCTTTCA TTGAGTTCCT 1380 TTCCTCTGGG AGGACTGGGG GTTGTCTAGC CCTCCACAGC ATCAGCCCAT TGACCCTATC 1440 CTTGTGGTTA TAGCAGCTGA GGAAGCAGAA TTACAGCTCT GTGGGAAGGA ATGGGGCTGG 1500 AGAGTTCATG CATAGACCAA TTCTTTTTTT TTTTTTTTTT TGAGATGGAG TTTCACTTTT 1560 GTTGCCCAGG CTGGAGTGCA ATGGCATGAT CTCAGCTCAC CACAGCCCCC ACCTCCTGGG 1620 TTCAAGCGAT TCTCCTGCCC TCAGCCTCCC GAGTAGCTGG GATTACAGGC ATGTGCCACC 1680 ACGCCTGACT ACTTTTGTAT TTTTAGTAGA GATGGAGTTT CTCTTTCTTG GTCAGGTTGG 1740 TCTCAAACTC CTGACCTCAG GTGATCTGCA GCCTCGGCCT CCAAAGTGTT GGGATTACAG 1800 GTGTGAGCGA CCATGCCTGG CTGCATAGAC CAGTTCTTAT GAGAAGGGAT CAACTAAGAA 1860 TAGCCTTGGG TTGACACACA CCCCTCTTCA CACTCACAGG AGAAACCCCA TGAAGCTAGA 19~9 ACCAGTCATG AGTTGAGAGC TGAGAGTTAG AGAGTAGCTC AGAGATGCTA TTCTTGGATA 1 .j TCCTGAGCCC CTGTGGTCAC CAGGGACCCT GAGTTGTGCA ACACTCAGCA TGACAGCATC 2040 ACTACACTTA AAAATTTCCC TCCTCACCCC CAGATTCCAT TTCCCCATCC GCCAGGGCTG 2100 CCTATAAAGA GGAGAGATGG CTTCAGACAT CAGAAGGACG CAGGCAGCAA AGAGTAGTCA 2160 GTCCCTTCTT GGCTCTGCTG ACACTCGAGC CCACATTCCA TCACCTGCTC CCAATCATGC 2220 AGGTCTCCAC TGCTGCCCTT GCCGTCCTCC TCTGCACCAT GGCTCTCTGC AACCAGGTCC 2280 TCTCTGCACC ACGTGAGTCC ATGTTGTTGT TGTGGGTATC ACCACTCTCT GGCCATGGTT 2340 AGACCACATC AGTCTTTTTT TGTGGCGTGA GAGGCCCCGA AGAGAAAAGA AGGAAGTTCT 2400 TAAAGCGCTG CCAAACACCT TGGTCTTTTT CTTCACAACT TTTATTTTTA TCTCTAGAAG 2460 GGGTCTTAGC CCTCCTAGTC TCCAGGTATG AGAATCTAGG CAGGGGCAGG GGAGTTACAG 2520 TCCCTTGTAC AGATAGAAAA ACAGGGTTCA AAACGAATCA GTTTGCAAGA GGCAGAATCC 2580 AGGGCTGCTT ACTTCCCAGT GGGGTCTGTT CTTCACTCTC CAGCTCACCC TAGTCTCCCA 2640 GGAGCCCTGT CCCTTGGATG TCTTATGAGA GATGTCCAGG GCTTCTCTTG GGCTGGGGTA 2700 TGACTTCTTG AACCGACAAA ATTCCATGAA GAGAGCTAAG AGAACAGTCC ATTCAGGTAT 2760 CTGGATCACA TAGAGAAACA GAGAACCCAC TATGAAGAGT CAAGGGGAAA GAGGAATATA 2820 GACAGAAACA AAGAGACATT TCTCTGCAAA ACCCCCCAAA TGCCTTGCAG TCACTTGGTC 2880 TGAGCAAGCC TGCCCTCCTC AACCACTCAG GGATCAGAAG CTGCCTGGCC TTTTCTTCTG 2940 AGCTGTGACT TGGGCTTATT CTCTCCTTTC TCCGCAGTTG CTGCTGACAC GCCGACCGCC 3000 TGCTGCTTCA GCTACACCTC CCGACAGATT CCACAGAATT TCATAGCTGA CTACTTTGAG 3060 ACGAGCAGCC AGTGCTCCAA GCCCAGTGTC ATGTAAGTGC CAGTCTTCCT GCTCACCTCT 3120 AGGGAGGTAG GGAGTGTCAG GGTGGGGGCA GAAACAGGCC AGAAGGCCAT CCTGGAAAGG 3180 CCCAGCCTTC AGGAGCCTAT CGGGGATACA GGACGCAGGG CACTGAGGTG TGACCTGACT 3240 TGGGGCTGGA GTGAGGTGGG TGTTACAGAG TCAGGAAGGG CTGCCCCAGG CCAGAGGAAA 3300 GGGACAGGAA GAAGGAGGCA GCAGGACACT CTGAGGGCCC CCTTGCCTGG AGTCACTGAG 3360 AGAAGCTCTC TAGACGGAGA TAGGCAGGGG GCCCCTGAGA GAGGAGCAGG CCTTGAGCTG 3420 CCCAGGACAG AGAGCAGGAT GTCAGGGCCA TGGTGGGCCC AGGATTCCCC GGCTGGATTC 3480 CCCAGTGCTT AACTCTTCCT CCCTTCTCCA CAGCTTCCTA ACCAAGAGAG GCCGGCAGGT 3540 CTGTGCTGAC CCCAGTGAGG AGTGGGTCCA GAAATACGTC AGTGACCTGG AGCTGAGTGC 3600 CTGAGGGGTC CAGAAGCTTC GAGGCCCAGC GACCTCAGTG GGCCCAGTGG GGAGGAGCAG 3660 GAGCCTGAGC CTTGGGAACA TGCGTGTGAC CTCCACAGCT ACCTCTTCTA TGGACTGGTT 3720 ATTGCCAAAC AGCCACACTG TGGGACTCTT CTTAACTTAA ATTTTAATTT ATTTATACTA 3780 TTTAGTTTTT ATAATTTATT TTTGATTTCA CAGTGTGTTT GTGATTGTTT GCTCTGAGAG 3840 TTCCCCCTGT CCCCTCCACC TTCCCTCACA GTGTGTCTGG TGACAACCGA GTGGCTGTCA 3900 TCGGCCTGTG TAGGCAGTCA TGGCACCAAA GCCACCAGAC TGACAAATGT GTATCAGATG 3960 CTTTTGTTCA GGGCTGTGAT CGGCCTGGGG AAATAATAAA GATGTTCTTT TAAACGGTAA 4020 ACCAGTATTG AGTTTGGTTT TGTTTTTCTG GCAAATCAAA ATCACTGGTT AAGAGGAATC 4080 ATAGGCAAAG ATTAGGAAGA GGTGAAATGG AGGGAAATTG GGAGAGATGG GGAGCGCTGC 4140 GACAGAGTTA TCCACTTCAC AAAATTCTGG AACATTGAAA CTACGAATAT GTTATAACTC 4200 AAATCGTAAT ATGCACGCTC TAGGAGAATT AACTACTTGA ATGGCCACCA TTAAGCAGAG 4260 TATTCTGTAG GGCATATTCA TGATGAATCA AGCTCTTAAT AGCAATTATT TACATTGTTG 4320 AGGCTTACTC CTCCTACTGA GTGCTTTTTA TACATTGTTC ATTTAATCTT ACCAATGCAA 4380 TAGTACAGCT TAGGTACTAT TAATACCTCC ACTTGACAGA AAAGTAACCC AGGGCTCAGA 4440 AAGGTTAGAC AACTTGGCTG AGGTTACACA GCACGTAAAC GGTCAATTGT GTTCCAAAAC 4500 TGGACTTTTA TTGAACTACA GACTATGCTG TTAACCATTG ACCAAGTTAT TTCCCAAAGT 4560 ATGACCCGCC TATACTCAAA TCTTACCCCA TTCTTTAACA GATGATACTT TATCCATTGC 4620 AACCACTTCC TGTCAGGATT CTGAGTTGAC ATAGAGTGTT TCAGCAGTGA TTATTTAAGC 4680 CAATTACATC AGGATCTTTA GGTGTAGACC TGGGAACTGA TATTTTTATC AAGCTCATGA 4740 GGTGTTCCAT AGCATGTTAA TGACTGAGAG CCACTGTCAA TAGAATTC 4788 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 92 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: Met Lys Leu Cys Val Thr Val Leu Ser Leu Leu Met Leu Val Ala Ala 1 5 10 15 Phe Cys Ser Pro Ala Leu Ser Ala Pro Met Gly Ser Asp Pro Pro Thr 20 25 30 Ala Cys Cys Phe Ser Tyr Thr Ala Arg Lys Leu Pro Arg Asn Phe Val 35 40 45 Val Asp Tyr Tyr Glu Thr Ser Ser Leu Cys Ser Gin Pro Ala Val Val 50 55 60 Phe Gin Thr Lys Arg Ser Lys Gin Val Cys Ala Asp Pro Ser Glu Ser 65 70 75 80 Trp Val Gin Glu Tyr Val Tyr Asp Leu Glu Leu Asn 85 90 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 696 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: TTCCCCCCCC CCCCCCCCCC CCCCGCCCGA GCACAGGACA CAGCTGGGTT CTGAAGCTTC 60 TGAGTTCTGC AGCCTCACCT CTGAGAAAAC CTCTTTTCCA CCAATACCAT GAAGCTCTGC 120 GTGACTGTCC TGTCTCTCCT CATGCTAGTA GCTGCCTTCT GCTCTCCAGC GCTCTCAGCA 180 CCAATGGGCT CAGACCCTCC CACCGCCTGC TGCTTTTCTT ACACCGCGAG GAAGCTTCCT 240 CGCAACTTTG TGGTAGATTA CTATGAGACC AGCAGCCTCT GCTCCCAGCC AGCTGTGGTA 300 TTCCAAACCA AAAGAAGCAA GCAAGTCTGT GCTGATCCCA GTGAATCCTG GGTCCAGGAG 360 TACGTGTATG ACCTGGAACT GAACTGAGCT GCTCAGAGAC AGGAAGTCTT CAGGGAAGGT 420 CACCTGAGCC CGGATGCTTC TCCATGAGAC ACATCTCCTC CATACTCAGG ACTCCTCTCC 480 GCAGTTCCTG TCCCTTCTCT TAATTTAATC TTTTTTATGT GCCGTGTTAT TGTATTAGGT 540 GTCATTTCCA TTATTTATAT TAGTTTAGCC AAAGGATAAG TGTCCTATGG GGATGGTCCA 600 CTGTCACTGT TTCTCTGCTG TTGCAAATAC ATGGATAACA CATTTGATTC TGTGTGTTTT 660 CCATAATAAA ACTTTAAAAT AAAATGCAGA CAGTTA 696 (2) INFORMATION FOR SEQ ID NO: 30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 96 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Met Gin He He Thr Thr Ala Leu Val Cys Leu Leu Leu Ala Gly Met 1 5 10 15 Trp Pro Glu Asp Val Asp Ser Lys Ser Met Gin Val Pro Phe Ser Arg 20 25 30 Cys Cys Phe Ser Phe Ala Glu Gin Glu He Pro Leu Arg Ala He Leu 35 40 45 Cys Tyr Arg Asn Thr Ser Ser He Cys Ser Asn Glu Gly Leu He Phe 50 55 60 Lys Leu Lys Arg Gly Lys Glu Ala Cys Ala Leu Asp Thr Val Gly Trp 65 70 75 80 Val Gin Arg His Arg Lys Met Leu Arg His Cys Pro Ser Lys Arg Lys 85 90 95 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 520 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31: ACCAGGCTCA TCAAAGCTGC TCCAGGAAGG CCCAAGCCAG ACCAGAAGAC ATGCAGATCA 60 TCACCACAGC CCTGGTGTGC TTGCTGCTAG CTGGGATGTG GCCGGAAGAT GTGGACAGCA 120 AGAGCATGCA GGTACCCTTC TCCAGATGTT GCTTCTCATT TGCGGAGCAA GAGATTCCCC 180 TGAGGGCAAT CCTGTGTTAC AGAAATACCA GCTCCATCTG CTCCAATGAG GGCTTAATAT 240 TCAAGCTGAA GAGAGGCAAA GAGGCCTGCG CCTTGGACAC AGTTGGATGG GTTCAGAGGC 300 ACAGAAAAAT GCTGAGGCAC TGCCCGTCAA AAAGAAAATG AGCAGATTTC TTTCCATTGT 360 GGGCTCTGGA AACCACATGG CTTCACCTGT CCCCGAAACT ACCAGCCCTA CACCATTCCT 420 TCTGCCCTGC TTTTGCTAGG TCACAGAGGA TCTGCTTGGT CTTGATAAGC TATGTTGTTG 480 CACTTTAAAC ATTTAAATTA TACAATCATC AACCCCCAAC 520 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 99 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu He Ala Ala Thr 1 5 10 15 Phe He Pro Gin Gly Lys Ala Gin Pro Asp Ala He Asn Ala Pro Val 20 25 30 Thr Cys Cys Tyr Asn Phe Thr Asn Arg Lys He Ser Val Gin Arg Leu 35 40 45 Ala Ser Tyr Arg Arg He Thr Ser Ser Lys Cys Pro Lys Glu Ala Val 50 55 60 He Phe Lys Thr He Val Ala Lys Glu He Cys Ala Asp Pro Lys Gin 65 70 75 80 Lys Trp Val Gin Asp Ser Met Asp His Leu Asp Lys Gin Thr Gin Thr 85 90 95 Pro Lys Thr (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 725 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: CTAACCCAGA AACATCCAAT TCTCAAACTG AAGCTCGCAC TCTCGCCTCC AGCATGAAAG 60 TCTCTGCCGC CCTTCTGTGC CTGCTGCTCA TAGCAGCCAC CTTCATTCCC CAAGGGCTCG 120 CTCAGCCAGA TGCAATCAAT GCCCCAGTCA CCTGCTGTTA TAACTTCACC AATAGGAAGA 180 TCTCAGTGCA GAGGCTCGCG AGCTATAGAA GAATCACCAG CAGCAAGTGT CCCAAAGAAG 240 CTGTGATCTT CAAGACCATT GTGGCCAAGG AGATCTGTGC TGACC( AAG CAGAAGTGGG 300 TTCAGGATTC CATGGACCAC CTGGACAAGC AAACCCAAAC TCCGAAGACT TGAACACTCA 360 CTCCACAACC CAAGAATCTG CAGCTAACTT ATTTTCCCCT AGCTTTCCCC AGACACCCTG 420 TTTTATTTTA TTATAATGAA TTTTGTTTGT TGATGTGAAA CATTATGCCT TAAGTAATGT 480 TAATTCTTAT TTAAGTTATT GATGTTTTAA GTTTATCTTT CATGGTACTA GTGTTTTTTA 540 GATACAGAGA CTTGGGGAAA TTGCTTTTCC TCTTGAACCA CAGTTCTACC CCTGGGATGT 600 TTTGAGGGTC TTTGCAAGAA TCATTAATAC AAAGAATTTT TTTTAACATT CCAATGCATT 660 GCTAAAATAT TATTGTGGAA ATGAATATTT TGTAACTATT ACACCAAATA AAT TATTTT 720 TGTAC 725 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 99 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: Met Lys Ala Ser Ala Ala Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala 1 5 10 15 Phe Ser Pro Gin Gly Leu Ala Gin Pro Val Gly He Asn Thr Ser Thr 20 25 30 Thr Cys Cys Tyr Arg Phe He Asn Lys Lys He Pro Lys Gin Arg Leu 35 40 45 Glu Ser Tyr Arg Arg Thr Thr Ser Ser His Cys Pro Arg Glu Ala Val 50 55 60 He Phe Lys Thr Lys Leu Asp Lys Glu He Cys Ala Asp Pro Thr Gin 65 70 75 80 Lys Trp Val Gin Asp Phe Met Lys His Leu Asp Lys Lys Thr Gin Thr 85 90 95 Pro Lys Leu (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 810 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: AGCAGAGGGG CTGAGACCAA ACCAGAAACC TCCAATTCTC ATGTGGAAGC CCATGCCCTC 60 ACCCTCCAAC ATGAAAGCCT CTGCAGCACT TCTGTGTCTG CTGCTCACAG CAGCTGCTTT 120 CAGCCCCCAG GGGCTTGCTC AGCCAGTTGG GATTAATACT TCAACTACCT GCTGCTACAG 180 ATTTATCAAT AAGAAAATCC CTAAGCAGAG GCTGGAGAGC TACAGAAGGA CCACCAGTAG 240 CCACTGTCCC CGGGAAGCTG TAATCTTCAA GACCAAACTG GACAAGGAGA TCTGTGCTGA 300 CCCCACACAG AAGTGGGTCC AGGACTTTAT GAAGCACCTG GACAAGAAAA CCCAAACTCC 360 AAAGCTTTGA ACATTCATGA CTGAACTAAA AACAAGCCAT GACTTGAGAA ACAAATAATT 420 TGTATACCCT GTCCTTTCTC AGAGTGGTTC TGAGATTATT TTAATCTAAT TCTAA UGAAT 480 ATGAGCTTTA TGTAATAATG TGAATCATGG TTTTTCTTAG TAGATTTTAA AAGTTATTAA 540 TATTTTAATT TAATCTTCCA TGGATTTTGG TGGGTTTTGA ACATAAAGCC TTGGATGTAT 600 ATGTCATCTC AGTGCTGTAA AAACTGTGGG ATGCTCCTCC CTTCTCTACC TCATGGGGGT 660 ATTGTATAAG TCCTTGCAAG AATCAGTGCA AAGATTTGCT TTAATTGTTA AGATATGATG 720 TCCCTATGGA AGCATATTGT TATTATATAA TTACATATTT GCATATGTAT GACTCCCAAA 780 TTTTCACATA AAATAGATTT TTGTAAAAAA 810 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 91 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: Met Lys Val Ser Ala Ala Arg Leu Ala Val He Leu He Ala Thr Ala 1 5 10 15 Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro 20 25 30 Cys Cys Phe Ala Tyr He Ala Arg Pro Leu Pro Arg Ala His He Lys 35 40 45 Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe 50 55 60 Val Thr Arg Lys Asn Arg Gin Val Cys Ala Asn Pro Glu Lys Lys Trp 65 70 75 80 Val Arg Glu Tyr He Asn Ser Leu Glu Met Ser 85 90 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1160 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: CCTCCGACAG CCTCTCCACA GGTACCATGA AGGTCTCCGC GGCACGCCTC GCTGTCATCC 60 TCATTGCTAC TGCCCTCTGC GCTCCTGCAT CTGCCTCCCC ATATTCCTCG GACACCACAC 120 CCTGCTGCTT TGCCTACATT GCCCGCCCAC TGCCCCGTGC CCACATCAAG GAGTATTTCT 180 ACACCAGTGG CAAGTGCTCC AACCCAGCAG TCGTCTTTGT CACCCGAAAG AACCGCCAAG 240 TGTGTGCCAA CCCAGAGAAG AAATGGGTTC GGGAGTACAT CAACTCTTTG GAGATGAGCT 300 AGGATGGAGA GTCCTTGAAC CTGAACTTAC ACAAATTTGC CTGTTTCTGC TTGCTCTTGT 360 CCTAGCTTGG GAGGCTTCCC CTCACTATCC TACCCCACCC GCTCCTTGAA GGGCCCAGAT 420 TCTGACCACG ACGAGCAGCA GTTACAAAAA CCTTCCCCAG GCTGGACGTG GTGGCTCAGC 480 CTTGTAATCC CAGCACTTTG GGAGGCCAAG GTGGGTGGAT CACTTGAGGT CAGGAGTTCG 540 AGACAGCCTG GCCAACATGA TGAAACCCCA TGTGTACTAA AAATACAAAA AATTAGCCGG 600 GCGTGGTAGC GGGCGCCTGT AGTCCCAGCT ACTCGGGAGG CTGAGGCAGG AGAATGGCGT 660 GAACCCGGGA GCGGAGCTTG CAGTGAGCCG AGATCGCGCC ACTGCACTCC AGCCTGGGCG 720 ACAGAGCGAG ACTCCGTCTC AAAAAAAAAA AAAAAAAAAA AAAAAATACA AAAATTAGCC 780 GCGTGGTGGC CCACGCCTGT AATCCCAGCT ACTCGGGAGG CTAAGGCAGG AAAATTGTTT 840 GAACCCAGGA GGTGGAGGCT GCAGTGAGCT GAGATTGTGC CACTTCACTC CAGCCTGGGT 900 GACAAAGTGA GACTCCGTCA CAACAACAAC AACAAAAAGC TTCCCCAACT AAAGCCTAGA 960 AGAGCTTCTG AGGCGCTGCT TTGTCAAAAG GAAGTCTCTA GGTTCTGAGC TCTGGCTTTG 1020 CCTTGGCTTT GCAAGGGCTC TGTGACAAGG AAGGAAGTCA GCATGCCTCT AGAGGCAAGG 1080 AAGGGAGGAA CACTGCACTC TTAAGCTTCC GCCGTCTCAA CCCCTCACAG GAGCTTACTG 1140 GCAAACATGA AAAATCGGGG 1160 (2) INFORMATION FOR SEQ ID NO:38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 97 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: Met Arg He Ser Ala Thr Leu Leu Cys Leu Leu Leu He Ala Ala Ala 1 5 10 15 Phe Ser He Gin Val Trp Ala Gin Pro Asp Gly Pro Asn Ala Ser Thr 20 25 30 Cys Cys Tyr Val Lys Lys Gin Lys He Pro Lys Arg Asn Leu Lys Ser 35 40 45 Tyr Arg Arg He Thr Ser Ser Arg Cys Pro Trp Glu Ala Val He Phe 50 55 60 Lys Thr Lys Lys Gly Met Glu Val Cys Arg Glu Ala His Gin Lys Trp 65 70 75 80 Val Glu Glu Ala He Ala Tyr Leu Asp Met Lys Thr Pro Thr Pro Lys 85 90 95 Pro (2) INFORMATION FOR SEQ ID NO: 39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 593 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) -"POLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: ACTGAAGCCA GCTCTCTCAC TCTCTTTCTC CACCATGAGG ATCTCTGCCA CGCTTCTGTG 60 CCTGCTGCTC ATAGCCGCTG CTTTCAGCAT CCAAGTGTGG GCCCAACCAG ATGGGCCCAA 120 TGCATCCACA TGCTGCTATG TCAAGAAAC AAGATCCCC AAGAGGAATC TCAAGAGCTA 180 CAGAAGGATC ACCAGTAGTC GGTGTCCCTG GGAAGCTGTT ATCTTCAAGA CAAAGAAGGG 240 CATGGAAGTC TCTCGTGAAG CCCATCAGAA GTGGGTCGAG GAGGCTATAG CATACTTAGA 300 CATGAAAACC CCAACTCCAA AGCCTTGAAb AAATGTGCCT GAACAGAAAC CAACCTAGGA 360 GCCAAGAAGC AAAAATTCCT CACCGCTGTT CTTTCTGAGA ACTGTTGATG AAATGTGTTG 420 ATCACGGTCC TAAGGGATAG GAGCTGTCTG TAGGAATGTG AAACAGTCAC GCCTAAGGAA 480 TGGTCTTTAA GTTATTAATA TTTTTATTTA ATTAGCCATG TACTTTGGTG TGATTTGAAT 540 GTAAAGCTCT GGAGACCTCA TGTCACTTTA ACATTGTGTT AGCTGCAGAA TTC 593 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 72 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear ( ii ) MOLECULE TYPE : peptide (xi ) SEQUENCE DESCRIPTION : SEQ ID -JO : 40 : Asp Ser Val Ser He Phe He Thr Cys Cys Phe Asn Val He Asn Arg 1 5 10 15 Lys He Pro He Gin Arg Leu Glu Ser Tyr Thr Arg He Thr Asn He 20 25 30 Gin Cys Pro Lys Glu Ala Val He Phe Lys Thr Gly Lys Glu Val Cys 35 40 45 Ala Asp Pro Lyε Glu Arg Trp Val Arg Asp Ser Met Lys His Lys Asp 50 55 60 Gin He Phe Gin Asn Leu Lys Pro 65 70 (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: Asn Leu Ala Lys Gly Lys Glu Glu Ser Leu Asp Ser Asp Leu Cys 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 32 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide ( i) SEQUENCE DESCRIPTION: SEQ ID NO:42 Cys Asn Gin Val Glu Val He Ala Thr Leu Lys Asp Gly Arg Lys He 1 5 10 15 Cys Leu Asp Pro Asp Ala Pro Arg He Lys Lys He Val Gin Lys Lys 20 25 30 (2) INFORMATION FOR SEQ ID NO:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 96 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: TGCAACCAAG TCGAAGTGAT AGCCACACTG AAGGATGGGA GGAAAATCTG CCTGGACCCA 60 GATGCTCCCA GAATCAAGAA AATTGTACAG AAAAAA 96

Claims: CLAIMS We claim: 1. A method of screening for AHA compounds comprising the steps of: a) contacting a compound with radiolabeled heparin/heparan sulfate and heparanase; b) maintaining the compounds in contact with the radiolabeled heparin/heparan sulfate and heparanase for a time and under such conditions sufficient to allow inhibition of heparanase activity; c) detecting inhibition of heparanase activity (a compound that gives 50% inhibition at a concentration of 1 μM or less); and d) selecting compounds that inhibit heparanase activity. 2. A method according to claim 1 wherein Jie heparanase is recombinant. 3. A heparanase having an isoelectric point of less than 5.5 and possessing activity greater than 20 units heparanase activity per μg protein. 4. A heparanase according to Claim 3, having an isoelectric point of about 4.8 - 5.1. 5. A heparanase purified to apparent homogeneity, as in claim 3, prepared in the presence of reducing conditions and activated with transglutaminase, having an amino acid sequence selected from the group consisting of SEQ. ID NO: 1, SEQ. ID NO: 3, SEQ. ID NO: 5 or SEQ. ID NO: 7. 6. A heparanase purified to apparent homogeneity, as in claim 3, prepared in the presence of reducing conditions, having a" amino acid sequence of SEQ. ID NO: 1. 7. A heparanase purified to apparent homogeneity, as in claim 3, prepared in the presence of reducing conditions and activated with transglutaminase, having an amino acid sequence of SEQ. ID NO: 3. &. A heparanase according to Claim 4, purified to apparent homogeneity, prepared in the presence of reducing conditions and activated with transglutaminase. 9. A heparanase, as in claim 3, prepared by recombinant means, activated ith transglutaminase and having an amino acid sequence selected from the group consisting of SEQ. ID NO: 1, SEQ. ID NO: 3, SEQ. ID NO: 5 or SEQ. ID NO: 7. 10. A heparanase, as in claim 3, prepared by recombinant means, activated with transglutaminase and having an amino acid sequence of SEQ. ID NO: 1. 11. A heparanase, as in claim 3, prepared by recombinant means, activated with transglutaminase and having an amino acid sequence of SEQ. ID NO: 3. 12. A heparanase purified to apparent homogeneity, as in claim 3, prepared in the presence of reducing conditions and activated with transglutaminase, and having an amino acid sequence selected from the group consisting of SEQ. ID. NO: 12, SEQ. ID. NO: 14; SEQ. ID. NO: 16, SEQ. ID. NO: 18, SEQ. ED. NO: 20, SEQ. JD. NO: 22 and SEQ. ID. NO: 24. 13. A heparanase purified to apparent homogeneity, as in claim 3, prepared in the presence of reducing conditions and activated with transglutaminase, and having an amino acid sequence selected from the group consisting of SEQ. ID. NO: 26, SEQ. ID. NO: 28, SEQ. ID. NO: 30, SEQ. ID. NO: 32; SEQ. ID. NO: 34, SEQ. ID. NO: 36, SEQ. ID. NO: 38 and SEQ.ID. NO: 40. 14. A method according to claim 1 wherein the heparanase is purified to apparent homogeneity, prepared in the presence of reducing conditions and activated with transglutaminase, and having an amino acid sequence selected from the group consisting of SEQ. JD. NO: 12, SEQ. JD. NO: 14; SEQ. ID. NO: 16, SEQ. ID. NO: 18, SEQ. ID. NO: 20, SEQ. -D. NO: 22 and SEQ. ID. NO: 24. 15. A method according to claim 1 wherein the heparanase is purified to apparent homogeneity, prepared in the presence of reducing conditions and activated with transglutaminase, and having an amino acid sequence selected from the group consisting of SEQ. ID. NO: 26, SEQ. ID. NO: 28, SEQ. ID. NO: 30, SEQ. ID. NO: 32; SEQ. ID. NO: 34, SEQ. ID. NO: 36, SEQ. ID. NO: 38 and SEQ. ID. NO: 40. 16. A method according to claim 1 wherein the heparanase is purified to apparent homogeneity, prepared in the presence of reducing conditions and activated with transglutaminase, and having an amino acid sequence selected from the group consisting of SEQ. ID NO: 1, SEQ. ID NO: 3, SEQ. ID NO: 5 or SEQ. JD NO: 7. 17. A peptide having an amino acid sequence of SEQ. ID. NO: 42.

Inventors: HOOGWERF ARLENE J, LEDBETTER STEVEN R, HOOGWERF, ARLENE, J., LEDBETTER, STEVEN, R.
Applicants: HOOGWERF ARLENE J, LEDBETTER STEVEN R, UPJOHN CO, HOOGWERF, ARLENE, J., LEDBETTER, STEVEN, R., THE UPJOHN COMPANY
Application year: 1994
Main classification: C12Q1
IPC codes: C07K14, C12N9, C12N15, C12Q1